A Study on the Effect of Blue Light on Kidney Stone Formation in Rats via the Brain-Kidney Axis

A Study on the Effect of Blue Light on Kidney Stone Formation in Rats via the Brain-Kidney Axis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article A Study on the Effect of Blue Light on Kidney Stone Formation in Rats via the Brain-Kidney Axis Dao-Cheng Fang, Yuan-Yuan Hu, Chao Wang, Jie Fan, Hui Wen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4972575/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Jan, 2025 Read the published version in Scientific Reports → Version 1 posted 13 You are reading this latest preprint version Abstract Kidney stones, a common disease in urology, are formed by multiple factors, among which the brain-kidney axis may play an important role in the occurrence and development of kidney stones, although the specific mechanism remains to be elucidated. This study aims to investigate the effects of blue light on relevant metabolic indicators and oxidative stress status in rats with kidney stones through the brain-kidney axis. To this end, we established a rat model of kidney stones and intervened with blue light, comparing it with normal rats. We found that compared with kidney stone rats without blue light intervention, those receiving blue light intervention exhibited significantly increased levels of antidiuretic hormone, intensified oxidative stress response, and augmented stone formation. However, in normal rats, blue light intervention did not cause significant changes in the aforementioned indicators. In summary, this study indicates that under pathological conditions, blue light may promote the secretion of antidiuretic hormone in serum and enhance oxidative stress response in renal tissues by affecting the brain-kidney axis, thereby accelerating the formation of kidney stones in rats. Health sciences/Medical research Health sciences/Urology Blue light Brain-kidney axis Kidney stones Oxidative stress Figures Figure 1 Figure 2 Figure 3 Introduction Kidney stones, as a common urinary system disease, have shown an increasing incidence globally, posing a significant threat to public health [ 1 – 3 ]. Currently, multiple studies have revealed that the formation of kidney stones is a complex process influenced by various factors, including living environment, dietary habits, and metabolic diseases [ 4 – 6 ]. Among them, the brain-kidney axis plays a crucial role in kidney diseases and is an important physiological network that regulates kidney function. Abnormalities in this axis may induce the formation of kidney stones by affecting metabolic pathways [ 7 , 8 ]. Recent studies have found that, apart from traditional environmental factors, light, especially blue light, may have potential effects on human physiological functions [ 9 , 10 ]. Blue light is closely related to the human biological clock and metabolic regulation mechanisms. It can influence the brain through the mediation of retinal ganglion cells (RGCs) and further affect relevant physiological functions [ 11 , 12 ]. Therefore, we hypothesize that blue light may exert an impact on the kidneys through the brain-kidney axis by regulating brain function. Currently, there is limited research on the relationship between the brain-kidney axis and kidney stones. In light of this, the present study aims to explore how blue light affects the formation of kidney stones in rats through the brain-kidney axis by constructing a rat model of kidney stones, and to discuss its potential mechanisms of action. Materials and methods Laboratory animals All work was approved and implemented by the Animal Ethics Committee of Shanghai Jiao Tong University School of Medicine (2024SQ013) in accordance with the national and regional guidelines. All authors complied with the ARRIVE guidelines. Forty SPF-grade male SD rats, with an average weight of (210 ± 15) g, were provided by the Animal Center of Songjiang Research Institute Affiliated to Shanghai Jiao Tong University School of Medicine. These rats were housed in the laboratory of the Animal Experiment Center and underwent adaptive feeding for 7 days at a temperature range of 22 to 25°C and a relative humidity of 50–60%. This study was approved by the Animal Ethics Committee of Songjiang hospital affiliated to Shanghai jiaotong university school of medicine (2024SQ013). Materials and Instruments Malonaldehyde (MDA) assay kit (provided by Hefei Lair Biotechnology Co., Ltd.), superoxide dismutase (SOD) assay kit (also from Hefei Lair Biotechnology Co., Ltd.), oxalic acid (Oxa) detection kit (supplied by Shanghai Youxuan Biotechnology Co., Ltd.), a blue light laser device (from Shanghai Xilong Optoelectronic Technology Co., Ltd.), and a multi-functional full-wavelength microplate reader. Grouping and modeling of rats Forty rats were randomly divided into Group A, Group B, Group C, and Group D, with ten rats in each group. Rats in Group C and Group D were administered with 1% ethylene glycol + 2% ammonium chloride via gavage (2 mL per rat), while rats in Group A and Group B were given an equal volume of 0.9% saline solution via gavage. Rats in Group A and Group C received blue light exposure twice daily (1 hour each time) starting from the second day after gavage as an intervention, while rats in Group B and Group D were exposed to daylight (using the same method as described). After four weeks of continuous intervention, 24-hour urine samples were collected from the rats for urine-related indicator detection. The rats were euthanized by carbon dioxide asphyxiation, and their blood and kidney tissues were collected for subsequent detection of various indicators. The pathological changes of renal tissue were observed using Von Kossa staining The left kidney of the rat was excised and processed with normal saline, followed by fixation with 4% paraformaldehyde. Subsequently, the standard Von Kossa staining procedure was followed for staining. The pathological changes of renal tissue were observed in detail under an optical microscope, and the severity of these pathological changes was evaluated based on the quantitative score of calcium salt crystallization [ 13 ]. Detection of serum antidiuretic hormone (ADH) and urinary Ca 2+ and Oxa levels A 2ml sample of blood was collected from the abdominal aorta, centrifuged at 3500 r/min for 15 minutes, and sent to the clinical laboratory of our hospital for the detection of serum ADH. Urine was collected and centrifuged at 3500 r/min for 20 minutes, with urine Ca 2+ content detected using an automatic biochemical analyzer. The determination of urinary Oxa was conducted strictly according to the kit instructions. MDA and SOD levels were detected using the ELISA method The right kidney was homogenized to make a 10% homogenate, which was then centrifuged at 3500 r/min for 15 minutes. The supernatant was collected and processed according to the kit instructions. The wavelength of the microplate reader was set to read the optical density values, and the levels of MDA and SOD were detected. Statistical analysis SPSS 22.0 software was utilized for data analysis. All measurement data were expressed as mean ± standard deviation. For group comparisons, one-way ANOVA was employed, with the T-test used for pairwise comparisons. The Kruskal-Wallis test was applied when variances were inconsistent. Statistical significance was considered at P < 0.05. Results Von Kossa staining was used to observe pathological changes in renal tissue There were no significant pathological changes in the kidney tissues of rats in groups A and B, and no calcium salt crystals were observed. Compared to groups A and B, groups C and D exhibited varying degrees of renal tubule dilation, severe renal tubule damage and atrophy, inflammatory cell infiltration in the surrounding renal tubule tissue, and the formation of calcium oxalate crystals within the renal interstitium, which appeared brown due to calcium binding (as indicated by the black arrow in Fig. 1 ), and the calcium salt crystal scores were higher ( P < 0.05). Compared with group D, the calcium salt crystal score in the kidney tissue of group C was higher ( P < 0.05) (Fig. 1 , Fig. 2 ). Comparison of serum ADH and urinary Ca 2+ and Oxa levels in four groups of rats There were no significant differences in serum ADH and urinary Ca2+, Oxa levels between groups A and B. Compared with groups A and B, groups C and D had higher serum ADH and urinary Ca 2+ , Oxa levels ( P < 0.05). Compared with group D, group C had higher serum ADH and urinary Ca 2+ , Oxa levels ( P < 0.05) (Table 1 ). Table 1 The levels of serum ADH, urine Ca2+, and urine Oxa were compared across each group(mean ± standard deviation) Group Serum ADH/(ng/L) Urine Ca 2+ /(mmol/L) Urine Oxa(µmol/L) Group A 0.28 ± 0.06 1.50 ± 0.15 120.04 ± 15.39 Group B 0.36 ± 0.10 1.58 ± 0.13 131.04 ± 15.69 Group C 1.65 ± 0.33 # 3.93 ± 0.16 # 236.17 ± 22.05 # Group D 1.31 ± 0.29 #* 3.11 ± 0.20 #* 211.64 ± 23.97 #* Note: Compared with group A and B, # P < 0.05; Compared with group C, * P < 0.05. Comparison of MDA and SOD levels in kidney tissues of C, four groups of rats There were no significant differences in the levels of MDA and SOD in kidney tissues between groups A and B. Compared with groups A and B, groups C and D had lower SOD levels and higher MDA levels in kidney tissues ( P < 0.05). Compared with group D, group C had lower SOD levels and higher MDA levels in kidney tissues ( P < 0.05) (Fig. 3 ). Discussion Kidney stones are one of the most prevalent diseases in urology, potentially accompanied by abnormal kidney function, urinary tract infections, and other complications [ 2 ]. While the pathogenesis remains incompletely understood, the theory of multifactorial interaction, encompassing metabolic abnormalities, lifestyle habits, and physiological states, has been widely accepted [ 4 ]. With the deepening of related research, it has been found that the brain-kidney axis plays a role in kidney diseases [ 8 , 14 ]. The brain-kidney axis involves the interaction between the central nervous system and the kidneys, primarily mediated through the hypothalamus-pituitary gland and the renal sympathetic nervous system. The hypothalamus regulates the secretion of related hormones through the pituitary gland, which subsequently influences various kidney functions, such as blood flow, filtration rate, and sodium excretion. The renal sympathetic nervous system regulates renal blood vessels, thereby affecting blood flow and urine production [ 14 ]. The paraventricular nucleus (PVN) within the hypothalamus serves as a pivotal node for information output from the hypothalamus [ 15 ], utilizing neuroendocrine neurons to modulate both the endocrine and autonomic nervous systems, thereby influencing metabolism. Both the supraoptic nucleus (SON) and PVN play crucial roles in renal water-salt balance, neuroregulation, and endocrine function. The large neurosecretory cells in the SON and PVN synthesize ADH, which is released in response to elevated plasma osmotic pressure, acts on the renal collecting ducts, and regulates fluid metabolic balance [ 16 ]. This suggests that under pathological conditions, blue light can stimulate increased production of ADH by affecting the brain-kidney axis, thereby promoting the formation of kidney stones. Previously, it was believed that the central nervous system possessed immune privileges due to the blood-brain barrier; however, recent studies have revealed its significant interactions with the immune system [ 17 ]. Various cells within the nervous system, including microglia and astrocytes, are capable of releasing cytokines and chemokines, thereby stimulating inflammatory responses and oxidative stress. In studies using rat models of kidney injury, significant changes in neurotransmitter levels have been observed, which exert profound effects on multiple aspects of the body. Meanwhile, Toll-like receptors (TLRs) in innate immunity, particularly TLR2 and TLR4, are activated upon kidney damage, exerting important influences on the interaction between the brain and kidney. These receptors are closely related to local inflammation, neuronal damage, and the regulation of cytokine expression [ 18 ]. The results of this study indicate that, compared to group D, group C exhibited lower levels of SOD and higher levels of MDA. Therefore, blue light may play a significant role in the pathogenesis of kidney stones by inducing oxidative stress via the brain-kidney axis. Current research has shown that optical regulation plays a crucial role in the function of the brain-kidney axis [ 10 , 19 ]. The effects of light are not limited to visual guidance but also involve a series of non-visual effects. These non-visual effects are partially mediated by the recently discovered RGCs that are highly sensitive to blue light [ 11 ]. Their influence extends to a wide range of physiological processes, including hormone secretion, heart rate, sleep propensity, body temperature, and gene expression [ 20 ]. Upon further investigation, a novel type of photoreceptive cell, the intrinsically photosensitive retinal ganglion cell (ipRGC), was discovered. Although these special cells constitute only a small fraction of RGCs, they play a crucial role in multiple non-visual functions such as diurnal rhythms, sleep, and emotions [ 21 ]. Notably, research by Zhang et al. [ 22 ] further indicates that stimulating ipRGCs can influence the secretion of neurotransmitters in the hypothalamus. Additionally, further studies have found that under the same light intensity, short-wavelength light with a wavelength of approximately 460 nm (i.e., blue light) has a particularly significant stimulatory effect on brain nerves [ 12 ]. This study found that the calcium salt crystallization scores in kidney tissue, serum ADH, and urinary Ca 2+ and Oxa levels were higher in groups C and D than in groups A and B. Furthermore, the calcium salt crystallization scores in kidney tissue, serum ADH, and urinary Ca 2+ and Oxa levels were higher in group C than in group D. Compared with groups A and B, the SOD levels in kidney tissue were lower and MDA levels were higher in groups C and D ( P < 0.05). Compared with group D, the SOD levels in kidney tissue were lower and MDA levels were higher in group C, while there were no significant differences in the relevant data between groups A and B. These findings suggest that under pathological conditions, blue light may affect the level of ADH in the body through the brain-kidney axis and promote oxidative stress, thereby facilitating the formation of kidney stones. This observation is consistent with previous research conclusions regarding the role of ADH and oxidative stress in the formation of kidney stones [ 13 , 23 , 24 ]. Despite the absence of significant differences in the relevant data between Group A and Group B, the elevated levels of serum ADH, urine Ca 2+ , Oxa, and renal MDA observed in Group B compared to Group A suggest that blue light irradiation may not directly induce stone formation under physiological conditions but could potentially act as a promoting factor for stone growth. This finding offers a novel perspective on understanding the impact of blue light on kidney stone formation, highlighting the need to consider potential risks associated with blue light exposure, especially given the rapid technological advancements and widespread exposure to blue light in daily life. While this study preliminarily reveals the potential role of the brain-kidney axis in the formation of kidney stones, it still has certain limitations. Firstly, the sample size of the experiment is relatively insufficient. Secondly, this study does not delve deeply into the specific mechanisms of the brain-kidney axis in the pathogenesis of kidney stones, as well as how blue light exerts its effects through the brain-kidney axis. In summary, this study preliminarily confirms the potential role of the brain-kidney axis in the formation of kidney stones, laying a foundation for further research on its mechanisms. Conclusions This study established a rat model of kidney stones to investigate the impact of blue light on kidney stone formation via the brain-kidney axis, offering a novel perspective for understanding the complex mechanisms underlying this process. The results demonstrated that, compared to groups A, B, and D, group C exhibited a higher calcium salt crystallization score in kidney tissue, elevated serum ADH, urinary Ca²⁺, and Oxa levels, as well as increased MDA levels in kidney tissue, while SOD levels were significantly decreased. These findings suggest that blue light may expedite kidney stone formation by modulating the brain-kidney axis, stimulating ADH secretion, and enhancing oxidative stress responses. This research not only provides preliminary insights into the potential role of blue light in kidney stone formation but also lays an experimental foundation for further exploration of the brain-kidney axis in kidney diseases. Future studies should expand the sample size and delve deeper into the specific mechanisms through which blue light affects the brain-kidney axis, thereby facilitating the development of novel preventive and therapeutic strategies for kidney stones. Abbreviations RGCs Retinal ganglion cells MDA Malonaldehyde SOD Superoxide dismutase Oxa Oxalic acid ADH Antidiuretic hormone TLRs Toll-like receptors IpRGC Intrinsically photosensitive retinal ganglion cell Declarations Author contributions Dao-Cheng Fang, Yuan-Yuan Hu, and Chao Wang contributed equally to the work and wrote the main manuscript text; Jie Fan * and Hui Wen * are directors. Funding This work was supported by the Shanghai Songjiang District Science and Technology Research Project (No. 2023SJKJGG84). Data availability Since this research is funded by the Shanghai Songjiang District Science and Technology Research Project, the datasets generated and/or analyzed during the current study are not publicly available until the completion of this project. But are available from the corresponding author on reasonable request. Conflict of interest The authors declare that they have no confict of interest. Statement ofAnimal Rights This study was approved by the Animal Ethics Committee of Songjiang hospital affiliated to Shanghai jiaotong university school of medicine. References Zeng G, Mai Z, Xia S, et al. (2017). "Prevalence of kidney stones in China: an ultrasonography based cross-sectional study." BJU Int 120: 109-116. Sorokin I,Pearle MS (2018). "Medical therapy for nephrolithiasis: State of the art." Asian J Urol 5: 243-255. Singh P, Harris PC, Sas DJ, et al. (2022). "The genetics of kidney stone disease and nephrocalcinosis." Nat Rev Nephrol 18: 224-240. Wagner CA (2021). "Etiopathogenic factors of urolithiasis." Arch Esp Urol 74: 16-23. Wang Z, Zhang Y, Zhang J, et al. (2021). "Recent advances on the mechanisms of kidney stone formation (Review)." Int J Mol Med 48. Hocker SE (2017). "Renal Disease and Neurology." Continuum (Minneap Minn) 23: 722-743. Yang T, Richards EM, Pepine CJ, et al. (2018). "The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease." Nat Rev Nephrol 14: 442-456. Ghoshal S (2023). "Renal and Electrolyte Disorders and the Nervous System." Continuum (Minneap Minn) 29: 797-825. Johns EJ, Kopp UC, DiBona GF (2011). "Neural control of renal function." Compr Physiol 1: 731-67. Osborn JW, Tyshynsky R, Vulchanova L (2021). "Function of Renal Nerves in Kidney Physiology and Pathophysiology." Annu Rev Physiol 83: 429-450. Vandewalle G, Maquet P, Dijk DJ (2009). "Light as a modulator of cognitive brain function." Trends Cogn Sci 13: 429-38. Antemie RG, Samoila OC, Clichici SV (2023). "Blue Light-Ocular and Systemic Damaging Effects: A Narrative Review." Int J Mol Sci 24. Yang H, Cheng X,Chen Y, et al. (2024). "Preliminary study of the role of nanobacteria in the formation of renal stones in experimental rats and its mechanism." Arch Med Sci Atheroscler Dis 9: e1-e15. Ariton DM, Jimenez-Balado J, Maisterra O, et al. (2021). "Diabetes, Albuminuria and the Kidney-Brain Axis." J Clin Med 10. Wen S, Wang C, Gong M, et al. (2019). "An overview of energy and metabolic regulation." Sci China Life Sci 62: 771-790. Uvnas-Moberg K, Gross MM, Calleja-Agius J, et al. (2024). "The Yin and Yang of the oxytocin and stress systems: opposites, yet interdependent and intertwined determinants of lifelong health trajectories." Front Endocrinol (Lausanne) 15: 1272270. Salvador A,Kipnis J (2022). "Immune response after central nervous system injury." Semin Immunol 59: 101629. Liu CC, Yamazaki Y, Heckman MG, et al. (2020). "Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer's disease." Alzheimers Dement 16: 1372-1383. Bedrosian TA, Nelson RJ (2017). "Timing of light exposure affects mood and brain circuits." Transl Psychiatry 7: e1017. Gronfier C (2014). "[Circadian clock and non-visual functions: the role of light in humans]." Biol Aujourdhui 208: 261-7. Mure LS (2021). "Intrinsically Photosensitive Retinal Ganglion Cells of the Human Retina." Front Neurol 12: 636330. Zhang Z, Liu WY, Diao YP, et al. (2019). "Superior Colliculus GABAergic Neurons Are Essential for Acute Dark Induction of Wakefulness in Mice." Curr Biol 29: 637-644.e3. Kavouras SA, Suh HG, Vallet M, et al. (2021). "Urine osmolality predicts calcium-oxalate crystallization risk in patients with recurrent urolithiasis." Urolithiasis 49: 399-405. Wang Z, Liu L, Li CY, et al. (2024). "Carboxymethylated Rhizoma alismatis polysaccharides reduces the risk of calcium oxalate stone formation by reducing cellular inflammation and oxidative stress." Urolithiasis 52: 63. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 30 Jan, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 26 Nov, 2024 Reviews received at journal 25 Nov, 2024 Reviewers agreed at journal 01 Nov, 2024 Reviews received at journal 18 Oct, 2024 Reviewers agreed at journal 14 Oct, 2024 Reviews received at journal 12 Oct, 2024 Reviewers agreed at journal 07 Oct, 2024 Reviewers agreed at journal 05 Oct, 2024 Reviewers invited by journal 05 Oct, 2024 Editor assigned by journal 05 Oct, 2024 Editor invited by journal 06 Sep, 2024 Submission checks completed at journal 04 Sep, 2024 First submitted to journal 25 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4972575","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":361914511,"identity":"b36a9fa7-55e8-4f84-a0ff-ea190bb1a29b","order_by":0,"name":"Dao-Cheng 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(×400).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4972575/v1/294f9947775bbbb77f01a2c0.png"},{"id":65945674,"identity":"51e1b949-e446-4c01-9428-a972b4e8f6bd","added_by":"auto","created_at":"2024-10-04 17:36:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":18943,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of calcium salt crystallization integral of rats in each group (mean ± standard deviation).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4972575/v1/d26e24492ae23f054dda7c15.png"},{"id":65946036,"identity":"a28c7ff1-d1bf-4d1f-b243-c92d4cea6133","added_by":"auto","created_at":"2024-10-04 17:44:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":33818,"visible":true,"origin":"","legend":"\u003cp\u003eA comparison was made of the levels of MDA and SOD in renal tissue of rats across each group (mean ± standard deviation).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4972575/v1/266e8cea32c201aaeb607659.png"},{"id":75351175,"identity":"8f5cf706-9fb8-43e0-ad32-ce930bc93b17","added_by":"auto","created_at":"2025-02-03 16:07:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":844380,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4972575/v1/9db5be02-467c-4e8b-beb7-2284823d2391.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Study on the Effect of Blue Light on Kidney Stone Formation in Rats via the Brain-Kidney Axis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eKidney stones, as a common urinary system disease, have shown an increasing incidence globally, posing a significant threat to public health [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Currently, multiple studies have revealed that the formation of kidney stones is a complex process influenced by various factors, including living environment, dietary habits, and metabolic diseases [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Among them, the brain-kidney axis plays a crucial role in kidney diseases and is an important physiological network that regulates kidney function. Abnormalities in this axis may induce the formation of kidney stones by affecting metabolic pathways [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecent studies have found that, apart from traditional environmental factors, light, especially blue light, may have potential effects on human physiological functions [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Blue light is closely related to the human biological clock and metabolic regulation mechanisms. It can influence the brain through the mediation of retinal ganglion cells (RGCs) and further affect relevant physiological functions [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Therefore, we hypothesize that blue light may exert an impact on the kidneys through the brain-kidney axis by regulating brain function. Currently, there is limited research on the relationship between the brain-kidney axis and kidney stones. In light of this, the present study aims to explore how blue light affects the formation of kidney stones in rats through the brain-kidney axis by constructing a rat model of kidney stones, and to discuss its potential mechanisms of action.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eLaboratory animals\u003c/h2\u003e \u003cp\u003e All work was approved and implemented by the Animal Ethics Committee of Shanghai Jiao Tong University School of Medicine (2024SQ013) in accordance with the national and regional guidelines. All authors complied with the ARRIVE guidelines. Forty SPF-grade male SD rats, with an average weight of (210\u0026thinsp;\u0026plusmn;\u0026thinsp;15) g, were provided by the Animal Center of Songjiang Research Institute Affiliated to Shanghai Jiao Tong University School of Medicine. These rats were housed in the laboratory of the Animal Experiment Center and underwent adaptive feeding for 7 days at a temperature range of 22 to 25\u0026deg;C and a relative humidity of 50\u0026ndash;60%. This study was approved by the Animal Ethics Committee of Songjiang hospital affiliated to Shanghai jiaotong university school of medicine (2024SQ013).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eMaterials and Instruments\u003c/h2\u003e \u003cp\u003eMalonaldehyde (MDA) assay kit (provided by Hefei Lair Biotechnology Co., Ltd.), superoxide dismutase (SOD) assay kit (also from Hefei Lair Biotechnology Co., Ltd.), oxalic acid (Oxa) detection kit (supplied by Shanghai Youxuan Biotechnology Co., Ltd.), a blue light laser device (from Shanghai Xilong Optoelectronic Technology Co., Ltd.), and a multi-functional full-wavelength microplate reader.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003eGrouping and modeling of rats\u003c/h2\u003e \u003cp\u003eForty rats were randomly divided into Group A, Group B, Group C, and Group D, with ten rats in each group. Rats in Group C and Group D were administered with 1% ethylene glycol\u0026thinsp;+\u0026thinsp;2% ammonium chloride via gavage (2 mL per rat), while rats in Group A and Group B were given an equal volume of 0.9% saline solution via gavage. Rats in Group A and Group C received blue light exposure twice daily (1 hour each time) starting from the second day after gavage as an intervention, while rats in Group B and Group D were exposed to daylight (using the same method as described). After four weeks of continuous intervention, 24-hour urine samples were collected from the rats for urine-related indicator detection. The rats were euthanized by carbon dioxide asphyxiation, and their blood and kidney tissues were collected for subsequent detection of various indicators.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003eThe pathological changes of renal tissue were observed using Von Kossa staining\u003c/h2\u003e \u003cp\u003eThe left kidney of the rat was excised and processed with normal saline, followed by fixation with 4% paraformaldehyde. Subsequently, the standard Von Kossa staining procedure was followed for staining. The pathological changes of renal tissue were observed in detail under an optical microscope, and the severity of these pathological changes was evaluated based on the quantitative score of calcium salt crystallization [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eDetection of serum antidiuretic hormone (ADH) and urinary Ca\u003csup\u003e2+\u003c/sup\u003e and Oxa levels\u003c/h2\u003e \u003cp\u003eA 2ml sample of blood was collected from the abdominal aorta, centrifuged at 3500 r/min for 15 minutes, and sent to the clinical laboratory of our hospital for the detection of serum ADH. Urine was collected and centrifuged at 3500 r/min for 20 minutes, with urine Ca\u003csup\u003e2+\u003c/sup\u003e content detected using an automatic biochemical analyzer. The determination of urinary Oxa was conducted strictly according to the kit instructions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eMDA and SOD levels were detected using the ELISA method\u003c/h2\u003e \u003cp\u003eThe right kidney was homogenized to make a 10% homogenate, which was then centrifuged at 3500 r/min for 15 minutes. The supernatant was collected and processed according to the kit instructions. The wavelength of the microplate reader was set to read the optical density values, and the levels of MDA and SOD were detected.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eSPSS 22.0 software was utilized for data analysis. All measurement data were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. For group comparisons, one-way ANOVA was employed, with the T-test used for pairwise comparisons. The Kruskal-Wallis test was applied when variances were inconsistent. Statistical significance was considered at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eVon Kossa staining was used to observe pathological changes in renal tissue\u003c/h2\u003e \u003cp\u003eThere were no significant pathological changes in the kidney tissues of rats in groups A and B, and no calcium salt crystals were observed. Compared to groups A and B, groups C and D exhibited varying degrees of renal tubule dilation, severe renal tubule damage and atrophy, inflammatory cell infiltration in the surrounding renal tubule tissue, and the formation of calcium oxalate crystals within the renal interstitium, which appeared brown due to calcium binding (as indicated by the black arrow in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), and the calcium salt crystal scores were higher (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Compared with group D, the calcium salt crystal score in the kidney tissue of group C was higher (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eComparison of serum ADH and urinary Ca\u003csup\u003e2+\u003c/sup\u003e and Oxa levels in four groups of rats\u003c/h2\u003e \u003cp\u003eThere were no significant differences in serum ADH and urinary Ca2+, Oxa levels between groups A and B. Compared with groups A and B, groups C and D had higher serum ADH and urinary Ca\u003csup\u003e2+\u003c/sup\u003e, Oxa levels (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Compared with group D, group C had higher serum ADH and urinary Ca\u003csup\u003e2+\u003c/sup\u003e, Oxa levels (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe levels of serum ADH, urine Ca2+, and urine Oxa were compared across each group(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSerum ADH/(ng/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUrine Ca\u003csup\u003e2+\u003c/sup\u003e/(mmol/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUrine Oxa(\u0026micro;mol/L)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e120.04\u0026thinsp;\u0026plusmn;\u0026thinsp;15.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e131.04\u0026thinsp;\u0026plusmn;\u0026thinsp;15.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e236.17\u0026thinsp;\u0026plusmn;\u0026thinsp;22.05\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003csup\u003e#*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003csup\u003e#*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e211.64\u0026thinsp;\u0026plusmn;\u0026thinsp;23.97\u003csup\u003e#*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: Compared with group A and B, \u003csup\u003e#\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Compared with group C, *\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eComparison of MDA and SOD levels in kidney tissues of\u003c/b\u003e C,\u003cb\u003efour groups of rats\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThere were no significant differences in the levels of MDA and SOD in kidney tissues between groups A and B. Compared with groups A and B, groups C and D had lower SOD levels and higher MDA levels in kidney tissues (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Compared with group D, group C had lower SOD levels and higher MDA levels in kidney tissues (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eKidney stones are one of the most prevalent diseases in urology, potentially accompanied by abnormal kidney function, urinary tract infections, and other complications [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. While the pathogenesis remains incompletely understood, the theory of multifactorial interaction, encompassing metabolic abnormalities, lifestyle habits, and physiological states, has been widely accepted [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. With the deepening of related research, it has been found that the brain-kidney axis plays a role in kidney diseases [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The brain-kidney axis involves the interaction between the central nervous system and the kidneys, primarily mediated through the hypothalamus-pituitary gland and the renal sympathetic nervous system. The hypothalamus regulates the secretion of related hormones through the pituitary gland, which subsequently influences various kidney functions, such as blood flow, filtration rate, and sodium excretion. The renal sympathetic nervous system regulates renal blood vessels, thereby affecting blood flow and urine production [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The paraventricular nucleus (PVN) within the hypothalamus serves as a pivotal node for information output from the hypothalamus [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], utilizing neuroendocrine neurons to modulate both the endocrine and autonomic nervous systems, thereby influencing metabolism. Both the supraoptic nucleus (SON) and PVN play crucial roles in renal water-salt balance, neuroregulation, and endocrine function. The large neurosecretory cells in the SON and PVN synthesize ADH, which is released in response to elevated plasma osmotic pressure, acts on the renal collecting ducts, and regulates fluid metabolic balance [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This suggests that under pathological conditions, blue light can stimulate increased production of ADH by affecting the brain-kidney axis, thereby promoting the formation of kidney stones.\u003c/p\u003e \u003cp\u003ePreviously, it was believed that the central nervous system possessed immune privileges due to the blood-brain barrier; however, recent studies have revealed its significant interactions with the immune system [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Various cells within the nervous system, including microglia and astrocytes, are capable of releasing cytokines and chemokines, thereby stimulating inflammatory responses and oxidative stress. In studies using rat models of kidney injury, significant changes in neurotransmitter levels have been observed, which exert profound effects on multiple aspects of the body. Meanwhile, Toll-like receptors (TLRs) in innate immunity, particularly TLR2 and TLR4, are activated upon kidney damage, exerting important influences on the interaction between the brain and kidney. These receptors are closely related to local inflammation, neuronal damage, and the regulation of cytokine expression [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The results of this study indicate that, compared to group D, group C exhibited lower levels of SOD and higher levels of MDA. Therefore, blue light may play a significant role in the pathogenesis of kidney stones by inducing oxidative stress via the brain-kidney axis. Current research has shown that optical regulation plays a crucial role in the function of the brain-kidney axis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The effects of light are not limited to visual guidance but also involve a series of non-visual effects. These non-visual effects are partially mediated by the recently discovered RGCs that are highly sensitive to blue light [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Their influence extends to a wide range of physiological processes, including hormone secretion, heart rate, sleep propensity, body temperature, and gene expression [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Upon further investigation, a novel type of photoreceptive cell, the intrinsically photosensitive retinal ganglion cell (ipRGC), was discovered. Although these special cells constitute only a small fraction of RGCs, they play a crucial role in multiple non-visual functions such as diurnal rhythms, sleep, and emotions [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Notably, research by Zhang et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] further indicates that stimulating ipRGCs can influence the secretion of neurotransmitters in the hypothalamus. Additionally, further studies have found that under the same light intensity, short-wavelength light with a wavelength of approximately 460 nm (i.e., blue light) has a particularly significant stimulatory effect on brain nerves [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study found that the calcium salt crystallization scores in kidney tissue, serum ADH, and urinary Ca\u003csup\u003e2+\u003c/sup\u003e and Oxa levels were higher in groups C and D than in groups A and B. Furthermore, the calcium salt crystallization scores in kidney tissue, serum ADH, and urinary Ca\u003csup\u003e2+\u003c/sup\u003e and Oxa levels were higher in group C than in group D. Compared with groups A and B, the SOD levels in kidney tissue were lower and MDA levels were higher in groups C and D (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Compared with group D, the SOD levels in kidney tissue were lower and MDA levels were higher in group C, while there were no significant differences in the relevant data between groups A and B. These findings suggest that under pathological conditions, blue light may affect the level of ADH in the body through the brain-kidney axis and promote oxidative stress, thereby facilitating the formation of kidney stones. This observation is consistent with previous research conclusions regarding the role of ADH and oxidative stress in the formation of kidney stones [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Despite the absence of significant differences in the relevant data between Group A and Group B, the elevated levels of serum ADH, urine Ca\u003csup\u003e2+\u003c/sup\u003e, Oxa, and renal MDA observed in Group B compared to Group A suggest that blue light irradiation may not directly induce stone formation under physiological conditions but could potentially act as a promoting factor for stone growth. This finding offers a novel perspective on understanding the impact of blue light on kidney stone formation, highlighting the need to consider potential risks associated with blue light exposure, especially given the rapid technological advancements and widespread exposure to blue light in daily life.\u003c/p\u003e \u003cp\u003eWhile this study preliminarily reveals the potential role of the brain-kidney axis in the formation of kidney stones, it still has certain limitations. Firstly, the sample size of the experiment is relatively insufficient. Secondly, this study does not delve deeply into the specific mechanisms of the brain-kidney axis in the pathogenesis of kidney stones, as well as how blue light exerts its effects through the brain-kidney axis. In summary, this study preliminarily confirms the potential role of the brain-kidney axis in the formation of kidney stones, laying a foundation for further research on its mechanisms.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study established a rat model of kidney stones to investigate the impact of blue light on kidney stone formation via the brain-kidney axis, offering a novel perspective for understanding the complex mechanisms underlying this process. The results demonstrated that, compared to groups A, B, and D, group C exhibited a higher calcium salt crystallization score in kidney tissue, elevated serum ADH, urinary Ca\u0026sup2;⁺, and Oxa levels, as well as increased MDA levels in kidney tissue, while SOD levels were significantly decreased. These findings suggest that blue light may expedite kidney stone formation by modulating the brain-kidney axis, stimulating ADH secretion, and enhancing oxidative stress responses. This research not only provides preliminary insights into the potential role of blue light in kidney stone formation but also lays an experimental foundation for further exploration of the brain-kidney axis in kidney diseases. Future studies should expand the sample size and delve deeper into the specific mechanisms through which blue light affects the brain-kidney axis, thereby facilitating the development of novel preventive and therapeutic strategies for kidney stones.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eRGCs \u0026nbsp;\u0026nbsp;\u0026nbsp;Retinal ganglion cells\u003c/p\u003e\n\u003cp\u003eMDA \u0026nbsp;\u0026nbsp;\u0026nbsp;Malonaldehyde\u003c/p\u003e\n\u003cp\u003eSOD \u0026nbsp;\u0026nbsp; \u0026nbsp;Superoxide dismutase\u003c/p\u003e\n\u003cp\u003eOxa \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Oxalic acid\u003c/p\u003e\n\u003cp\u003eADH \u0026nbsp;\u0026nbsp; \u0026nbsp;Antidiuretic hormone\u003c/p\u003e\n\u003cp\u003eTLRs\u0026nbsp; \u0026nbsp;\u0026nbsp;Toll-like receptors\u003c/p\u003e\n\u003cp\u003eIpRGC \u0026nbsp;Intrinsically photosensitive retinal ganglion cell\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e Dao-Cheng Fang, Yuan-Yuan Hu, and Chao Wang contributed equally to the work and wrote the main manuscript text; Jie Fan\u003csup\u003e*\u003c/sup\u003e and Hui Wen\u003csup\u003e*\u003c/sup\u003e are directors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e This work was supported by the Shanghai Songjiang District Science and Technology Research Project (No. 2023SJKJGG84).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003eSince this research is funded by the Shanghai Songjiang District Science and Technology Research Project, the datasets generated and/or analyzed during the current study are not publicly available until the completion of this project. But are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e The authors declare that they have no confict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatement ofAnimal Rights\u0026nbsp;\u003c/strong\u003eThis study was approved by the Animal Ethics Committee of Songjiang hospital affiliated to Shanghai jiaotong university school of medicine.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eZeng G, Mai Z, Xia S, et al. (2017). \u0026quot;Prevalence of kidney stones in China: an ultrasonography based cross-sectional study.\u0026quot; BJU Int 120: 109-116.\u003c/li\u003e\n\u003cli\u003eSorokin I,Pearle MS (2018). \u0026quot;Medical therapy for nephrolithiasis: State of the art.\u0026quot; Asian J Urol 5: 243-255.\u003c/li\u003e\n\u003cli\u003eSingh P, Harris PC, Sas DJ, et al. (2022). \u0026quot;The genetics of kidney stone disease and nephrocalcinosis.\u0026quot; Nat Rev Nephrol 18: 224-240.\u003c/li\u003e\n\u003cli\u003eWagner CA (2021). \u0026quot;Etiopathogenic factors of urolithiasis.\u0026quot; Arch Esp Urol 74: 16-23.\u003c/li\u003e\n\u003cli\u003eWang Z, Zhang Y, Zhang J, et al. (2021). \u0026quot;Recent advances on the mechanisms of kidney stone formation (Review).\u0026quot; Int J Mol Med 48.\u003c/li\u003e\n\u003cli\u003eHocker SE (2017). \u0026quot;Renal Disease and Neurology.\u0026quot; Continuum (Minneap Minn) 23: 722-743.\u003c/li\u003e\n\u003cli\u003eYang T, Richards EM, Pepine CJ, et al. (2018). \u0026quot;The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease.\u0026quot; Nat Rev Nephrol 14: 442-456.\u003c/li\u003e\n\u003cli\u003eGhoshal S (2023). \u0026quot;Renal and Electrolyte Disorders and the Nervous System.\u0026quot; Continuum (Minneap Minn) 29: 797-825.\u003c/li\u003e\n\u003cli\u003eJohns EJ, Kopp UC, DiBona GF (2011). \u0026quot;Neural control of renal function.\u0026quot; Compr Physiol 1: 731-67.\u003c/li\u003e\n\u003cli\u003eOsborn JW, Tyshynsky R, Vulchanova L (2021). \u0026quot;Function of Renal Nerves in Kidney Physiology and Pathophysiology.\u0026quot; Annu Rev Physiol 83: 429-450.\u003c/li\u003e\n\u003cli\u003eVandewalle G, Maquet P, Dijk DJ (2009). \u0026quot;Light as a modulator of cognitive brain function.\u0026quot; Trends Cogn Sci 13: 429-38.\u003c/li\u003e\n\u003cli\u003eAntemie RG, Samoila OC, Clichici SV (2023). \u0026quot;Blue Light-Ocular and Systemic Damaging Effects: A Narrative Review.\u0026quot; Int J Mol Sci 24.\u003c/li\u003e\n\u003cli\u003eYang H, Cheng X,Chen Y, et al. (2024). \u0026quot;Preliminary study of the role of nanobacteria in the formation of renal stones in experimental rats and its mechanism.\u0026quot; Arch Med Sci Atheroscler Dis 9: e1-e15.\u003c/li\u003e\n\u003cli\u003eAriton DM, Jimenez-Balado J, Maisterra O, et al. (2021). \u0026quot;Diabetes, Albuminuria and the Kidney-Brain Axis.\u0026quot; J Clin Med 10.\u003c/li\u003e\n\u003cli\u003eWen S, Wang C, Gong M, et al. (2019). \u0026quot;An overview of energy and metabolic regulation.\u0026quot; Sci China Life Sci 62: 771-790.\u003c/li\u003e\n\u003cli\u003eUvnas-Moberg K, Gross MM, Calleja-Agius J, et al. (2024). \u0026quot;The Yin and Yang of the oxytocin and stress systems: opposites, yet interdependent and intertwined determinants of lifelong health trajectories.\u0026quot; Front Endocrinol (Lausanne) 15: 1272270.\u003c/li\u003e\n\u003cli\u003eSalvador A,Kipnis J (2022). \u0026quot;Immune response after central nervous system injury.\u0026quot; Semin Immunol 59: 101629.\u003c/li\u003e\n\u003cli\u003eLiu CC, Yamazaki Y, Heckman MG, et al. (2020). \u0026quot;Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer\u0026apos;s disease.\u0026quot; Alzheimers Dement 16: 1372-1383.\u003c/li\u003e\n\u003cli\u003eBedrosian TA, Nelson RJ (2017). \u0026quot;Timing of light exposure affects mood and brain circuits.\u0026quot; Transl Psychiatry 7: e1017.\u003c/li\u003e\n\u003cli\u003eGronfier C (2014). \u0026quot;[Circadian clock and non-visual functions: the role of light in humans].\u0026quot; Biol Aujourdhui 208: 261-7.\u003c/li\u003e\n\u003cli\u003eMure LS (2021). \u0026quot;Intrinsically Photosensitive Retinal Ganglion Cells of the Human Retina.\u0026quot; Front Neurol 12: 636330.\u003c/li\u003e\n\u003cli\u003eZhang Z, Liu WY, Diao YP, et al. (2019). \u0026quot;Superior Colliculus GABAergic Neurons Are Essential for Acute Dark Induction of Wakefulness in Mice.\u0026quot; Curr Biol 29: 637-644.e3.\u003c/li\u003e\n\u003cli\u003eKavouras SA, Suh HG, Vallet M, et al. (2021). \u0026quot;Urine osmolality predicts calcium-oxalate crystallization risk in patients with recurrent urolithiasis.\u0026quot; Urolithiasis 49: 399-405.\u003c/li\u003e\n\u003cli\u003eWang Z, Liu L, Li CY, et al. (2024). \u0026quot;Carboxymethylated Rhizoma alismatis polysaccharides reduces the risk of calcium oxalate stone formation by reducing cellular inflammation and oxidative stress.\u0026quot; Urolithiasis 52: 63.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Blue light, Brain-kidney axis, Kidney stones, Oxidative stress","lastPublishedDoi":"10.21203/rs.3.rs-4972575/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4972575/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Kidney stones, a common disease in urology, are formed by multiple factors, among which the brain-kidney axis may play an important role in the occurrence and development of kidney stones, although the specific mechanism remains to be elucidated. This study aims to investigate the effects of blue light on relevant metabolic indicators and oxidative stress status in rats with kidney stones through the brain-kidney axis. To this end, we established a rat model of kidney stones and intervened with blue light, comparing it with normal rats. We found that compared with kidney stone rats without blue light intervention, those receiving blue light intervention exhibited significantly increased levels of antidiuretic hormone, intensified oxidative stress response, and augmented stone formation. However, in normal rats, blue light intervention did not cause significant changes in the aforementioned indicators. In summary, this study indicates that under pathological conditions, blue light may promote the secretion of antidiuretic hormone in serum and enhance oxidative stress response in renal tissues by affecting the brain-kidney axis, thereby accelerating the formation of kidney stones in rats.","manuscriptTitle":"A Study on the Effect of Blue Light on Kidney Stone Formation in Rats via the Brain-Kidney Axis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-04 17:36:02","doi":"10.21203/rs.3.rs-4972575/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-26T06:06:05+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-25T10:43:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"253401122522822655040207356492508578897","date":"2024-11-01T08:28:14+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-18T05:06:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"145172299273238086004095199577495356201","date":"2024-10-14T13:04:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-12T17:48:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"112390325977048219559899473783764991253","date":"2024-10-07T06:49:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"227129778874647101464411760924195116257","date":"2024-10-06T02:39:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-10-06T01:55:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-06T01:53:37+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-09-06T04:01:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-09-04T07:33:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-08-25T12:02:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6031b0d8-6018-4f5a-898c-bdfbd62059bf","owner":[],"postedDate":"October 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":38503624,"name":"Health sciences/Medical research"},{"id":38503625,"name":"Health sciences/Urology"}],"tags":[],"updatedAt":"2025-02-03T16:00:01+00:00","versionOfRecord":{"articleIdentity":"rs-4972575","link":"https://doi.org/10.1038/s41598-025-85586-y","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-01-30 15:57:08","publishedOnDateReadable":"January 30th, 2025"},"versionCreatedAt":"2024-10-04 17:36:02","video":"","vorDoi":"10.1038/s41598-025-85586-y","vorDoiUrl":"https://doi.org/10.1038/s41598-025-85586-y","workflowStages":[]},"version":"v1","identity":"rs-4972575","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4972575","identity":"rs-4972575","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}