Catechin, Epicatechin and Quercetin against Gamma-irradiation- induced Nrf-2, Nf-kB and Antioxidant Enzymes alterations in Cellular System of Rats

Catechin, Epicatechin and Quercetin against Gamma-irradiation- induced Nrf-2, Nf-kB and Antioxidant Enzymes alterations in Cellular System of Rats | 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 Research Article Catechin, Epicatechin and Quercetin against Gamma-irradiation- induced Nrf-2, Nf-kB and Antioxidant Enzymes alterations in Cellular System of Rats Olamilekan Kabir BELLO, Musa Oyewole Salawu, Joseph Asuku Samuel, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4541075/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 3 You are reading this latest preprint version Abstract Background : Cell are prone to oxidative insults that are mediated by Rats exposure to gamma (γ) irradiation. These insult are nuclear factor kappa-B (Nf-kB) mediated, but the activation of nuclear related factor-2 (Nrf-2) renders cells resistant to oxidative insult and inflammatory challenges, mediated by Nf-kB. Plant materials have been used successfully to restore cellular alterations mediated by Nf-kB. Contain in these plants are catechin, epicatechin, astragalin and quercetin. Hence this study investigated the effects of catechin, epicatechin and quercetin against γ-irradiation-induced Nrf-2, Nf-kB and antioxidant enzymes alterations in Rats. Materials and Method: A total of thirty (30) rats (200 ± 5g) were distributed into 5 groups of 6 each. Except group 1, all other groups were exposed to 6 grey γ-irradiation. Group 2 were fed with rat chow and water only such that groups 3, 4 and 5 were administered catechin (CAT), epicatechin (EPC) and quercetin (QCT) at 40 mg/kg body weight respectively. The rats were sacrificed and biochemical parameters were assayed. Data were analyzed using SPSS. Results: Irradiation significantly (p<0.05) increased Nf-kB, reduced antioxidant enzymes activities, with a significant (p<0.05) decreased in Nrf-2 concentration of irradiated rats. Administration of CAT, EPC and QCT significantly (p<0.05) decreased Nf-kB and a corresponding significant (p<0.05) increased in Nrf-2 concentration and antioxidant enzymes activities of administered groups when compared with control. Conclusion: CAT, EPC and QCT have restored cellular alterations caused by γ-irradiation, hence can be used as protection against irradiation-induced alterations. Nf-kB Nrf-2 quercetin catechin epicatechin irradiation alteration antioxidant enzymes Figures Figure 1 Figure 2 Introduction The transcription factor Nf-kB serves as a pivotal mediator of inflammatory responses. [26] The switch-on of Nf-kB by free radicals induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokine and also participates in inflammasome regulation. [22] Consequently, deregulated Nf-kB activation contributes to various inflammatory diseases. [24] Reactive oxygen and nitrogen species (ROS/RNS) have been implicated in the activation of Nf-kB. [18] An exacerbated free radical level have been suggested to mediate an increased ROS/RNS in rats. An ROS/RNS level mediated the activation of inhibitory kappa-B kinase (ikk). ikk phosphorylate the Inhibitory kappa-B (ikB) component of the Nf-kB (the ikB is the repressor of Nf-kB in the cytosol), thus tag it for ubiquitination by the 26-s proteasome. Ubiquitination cleaved off the ikB component of Nf-kB to become active. [21] Activated Nf-kB is translocated to the nucleus where it bind the DNA binding region of the nucleus to express for inflammatory biomarkers such as cytokines, chemokine, prostaglandins etc. [19] All the expressed biomarkers are capable of causing cellular alterations in human system. [19] When Nf-kB is switched-off, there is possibility of having Nrf-2 switched-on. [14] Nuclear factor erythroid 2-related factor 2 (NrF-2) is a transcription factor that regulates the cellular defense against toxic and oxidative insults as well as defense against the synthesis of possible inflammatory biomarkers, usually through the expression of genes involved in oxidative stress response and drug detoxification. Nrf-2 activation renders cells resistant to chemical carcinogens and inflammatory challenges mediated by Nf-kB. [12] Increased consumption of natural products such as vegetables, fruits and many other non-toxic plant substances have been implicated in the activation of a cytosolically repressed (inactive) Nrf-2. [26] Contain in these natural plant materials are bioactive constituents like polyphenols, flavonoids, catechin, quercetin, tocopherol, epicatechin, luteolin and many more. They activate inactive Nrf-2 by mediating the phosphorylation of the keap-1(cytosolic repressor of Nrf-2). This phosphorylation tagged Nrf-2 for ubiquitination by the 26-s proteasome. [26] Ubiquitination eventually cleaved-off keap-1 from Nrf-2, to become an active Nrf-2. It translocate into the nucleus where it binds to the antioxidant responsive element (ARE) region of the DNA and thus expressed for antioxidant enzymes, phase-2 enzymes and anti-inflammatory proteins. [24] These proteins/enzymes are capable of defending the cell against pro and inflammatory insult as well as oxidative insult by ROS/RNS. [23] Increased ROS/RNS have been implicated in antioxidant enzymes depletion. [28] Hence an imbalance between ROS/RNS and the systemic antioxidant capacity is the underlying genesis of cellular alterations. [25] Nrf-2 have been directly linked with the expression of antioxidant enzymes, such that the higher the Nrf-2 activated, the more the antioxidant expressed, hence the more they are available to scavenge free radicals in cellular system. [26] Several scientific studies have validated the pathological implications of an activated Nf-kB mediated by an increased free radicals, ROS and RNS in experimental rats. Scientific claims have also validated the pharmacological advantages of activating Nrf-2 through the feeding/administration of plant materials experimental rat. [31] Have validated the solvent fractions of methanol leaves extracts of Adansonia digitata and Corchorus olitorius in gamma-irradiation-induced Nf-kB, Nrf-2 and antioxidant alterations in Rats. Another studies by [32] have validated the amelioration of radiation-induced cellular alterations in rat administered with solvent fractions of methanol leaf extracts of Adansonia digitata and Corchorus olitorius. These research work have established the influence of plant materials on the activation and inactivation of Nrf-2 and Nf-kB as well as how they altered cellular alterations. The work by [33] have established the several bioactive constituents of n-butanol subfractions of Adansonia digitata and Corchorus olitorius . Some of the bioactive constituents are catechin, epicatechin, luteolin, quercetin, astragalin etc. [33] However, the gap that is begging for attention is to successfully administered these bioactive constituents in these plants against irradiation-induced Nf-kB and Nrf-2 cellular alterations in rats. Hence this study aim to investigate the effect of catechin, epicatechin and quercetin against gamma-irradiation-induced Nf-kB and Nrf-2 alterations in cellular system of rats. Materials and Method 3.1 Experimental Animal A total of thirty (30), Wistar rats (200 ± 5.00 g) were obtained from the Animal Holding Unit of the Department of Biochemistry, University of Ilorin, Ilorin, Nigeria. The rats were housed in clean cages and well-ventilated house conditions (Temperature: 28.30ºC), (Photo-period; 12hr light, 12hr dark), (Humidity: 45-55%). They were fed with pelletized rats feed (Vital Feed, Grand Cereals, Jos, Nigeria) and clean tap water which were provided before and during administration. 3.2 Exposure of Rats to Radiation and Induction of Cellular Alteration in Rats Experimental rats were exposed to single dose of 6 grey whole-body gamma radiation by the method described by [28] and modified by. [34] The rats were kept in an improvised carton cage with holes made round the carton for ventilation (carton was used to restricts the movement and ensure uniform exposure of the rats to radiation) instead of the usual radiation exposure coat that was used by. [28] 3.3 Drugs, Chemicals and Assay Kits Nuclear Factor Kappa-B (Nf-kB) and nuclear related factor-2 (Nrf-2) enzyme linked immunoassay (ELISA) kits were products of Cayman Laboratory Limited, United State of America (USA). All chemicals used were all prepared in all-glass distilled water using standard procedures. 3.4 Preparation Catechin, Epicatechin and Quercetin Solution The 40 mg/kg body weight solutions of catechin, epicatechin and quercetin were prepared by the method described by [33] . 3.5. Table 1: Animal groupings and Administration Groups Administration Group 1 (Positive) Non-irradiated (NIR) Group 2 (Negative) Irradiated (IR) Group 3 (IR +CAT) IR + 40 mg/kg bwt Catechin Group 4 (IR + EPC) IR + 40 mg/kg bwt Epicatechin Group 5 (IR + QCT) IR + 40 mg/kg bwt Quercetin 3.6 . Animal sacrifice and nuclear extract preparation The rats in Table 1 were sacrificed by cervical dislocation, they were dissected and tissue (liver) were isolated. The 1.14 % KCL washing solution was used to rinse the liver off blood and other stains. About 1 g of the liver were homogenized in ice cold 0.25 M sucrose solution. The homogenate were cold-centrifuged at 12000 rpm. The supernatant were discarded and sediment were retained for the preparation of nuclear extract. 3.7 Preparation of nuclear extract The nuclear extract (from which Nf-kB and Nrf-2 were produced) was prepared by the method described by [31] . 3.8 Determination of Nf-kB and Nrf-2 Status of Irradiated Rats administered with Catechin, epicatechin and quercetin Nf-kB and Nrf-2 status were described by the method adopted by [35] 3.9. Table 2: Determination of the Antioxidant Enzymes Activities of Irradiated Rats, administered CAT, EPC and QCT Antioxidant Enzymes Procedures Superoxide Dismutase (SOD) According to method adopted by Haliwell et al . (2021) Catalase (CAT) According to method adopted by Yhong-sur (1989) Glutathione Transferase (GST) According to method adopted by Abolaji (2015) Glutathione Peroxidase (GPx) According to method adopted by Lazekhs et al. (1982b) Malondialdehyde (MDA) According to method adopted by Rice –Evans et al . (1986) 3.9.1 Ethical Approval Ethical approval was obtained from the University of Ilorin Ethical Committee, University of Ilorin. With the ethical approval number obtained as follow UERC/ASN/2018/1409 on the 13 th September, 2022. The study was conducted following the guidelines on the care and use of laboratory animals. 3.9 Statistical Analysis Data were expressed as mean ± SEM of 6 determinations except otherwise stated. All results were statistically analyzed using Duncan Multiple Range Test and complemented with Student’s t-test. Statistical Package for Social Sciences, version 21 (SPSS Inc., Chicago, IL, USA) were used for statistical analyses. Statistical significance was set at 95% confidence interval (Mahajan, 1997). Results 4.1 The effects of catechin, epicatechin and quercetin on Nf-kB Concentration of irradiated Rats 6 grey gamma irradiation have significantly (p<0.05) increased the concentration of Nf-kB in irradiated rats. Administration of catechin, epicatechin and quercetin have significantly (p<0.05) attenuate the level to that which favorably competed with the positive control. The competition was 100 % as shown in figure 1. 4.2 The effects of catechin, epicatechin and quercetin on Nrf-2 Concentration of irradiated Rats 6 grey gamma irradiation have significantly (p<0.05) increased the concentration of Nf-kB in irradiated rats. Administration of catechin, epicatechin and quercetin have significantly (p<0.05) attenuate the level to that which favorably competed with the positive control. The competition was 100 % as shown in figure 2. Table 3: The Effects of CAT, EPC and QCT on the Antioxidant Enzymes Activities of gamma irradiated Rats in µ g/ml/mg protein Groups SOD CAT GST GPX MDA Positive (NIR) 16.34 ± 0.54 a 21.56 ± 0.54 a 64.21± 0.54 a 42.20 ± 0.54 a 6.87 ± 0.54 a Negative (IR) 4.65 ± 0.54 b 8.90 ± 0.54 b 15.88 ± 0.54 b 12.21 ± 0.54 b 22.98± 0.54 b IR + CAT 19.89 ± 0.64 c 22.45 ± 0.14 a 71.2 ± 0.54 c 40.86 ± 0.54 a 5.34 ± 0.54 a IR + EPC 20.21 ± 0.51 c 21.98 ± 0.35 a 70.06 ± 0.54 c 41.21 ± 0.54 a 6.03 ± 0.54 a IR + QCT 20.22 ± 0.44 c 22.21 ± 0.54 a 72.02 ± 0.54 c 41.21 ± 0.54 a 6.15 ± 0.54 a Values are expressed as Means ± SEM; n=6 at (P<0.05); Values with same superscript are not significantly different, whereas those with different superscript are significantly different from each other. Discussion [34] have scientifically validated, that gamma radiation induced cellular alterations by increasing Nf-kB and reducing Nrf-2 concentration to a level that is capable of causing overexpression of pro and inflammatory biomarkers such as chemokines, cytokines prostaglandins as well as increasing the generation of ROS/RNS in irradiated rats. [24][19][34] . In the present study, the increased Nf-kB and decreased Nrf-2 concentration of irradiated rats as shown in Figure 1 and 2, have been associated with the 6 grey gamma irradiation, thus, leading to a depleted antioxidant enzymes activities in the irradiated rats. [32] Have scientifically established that n-butanol fraction of Adansonia digitata and Corchorous olitorous leaves is the most effective of the three fractions (n-hexane, ethylacetate and n-butanol fractions) tested against gamma irradiation-induced Nf-kB and Nrf-2 alterations in the cellular system of rats. [33] have also validated that the n-butanol subfractions 1 and 4 of Adansonia digitata and 2 and 3 of Corchorous olitorous are the most effective of the n-butanol subfractions against gamma irradiation-induced Nf-kB and Nrf-2 alterations in rats. The high performance liquid chromatography (HPLC) fingerprinting of the n-butanol subfractions 1 and 4 of Adansonia digitata and 2 and 3 Corchorous olitorous leaves revealed the presence of catechin, epicatechin, quercetin, astragalin, luteolin, eleagnin and polyunsaturated fatty acids. [32] These constituents in Adansonia digitata and Corchorous olitorous leaves maybe be responsible for their pharmacological action. In the present study, the groups of rats administered with CAT, EPC and QCT have significant (p<0.05) reduction in the level of Nf-kB and a corresponding significant increase in Nrf-2, suggesting that the CAT, EPC and QCT were able to restore the alteration in the irradiated rats system as shown in Figure 1 and 2 above. Irradiation induced free radical generation and by extension ROS/RNS. Increased free radical from a subtoxic to toxic level will overwhelmed the systemic antioxidant enzymes capacity to a level that eventually stressed the cell. During this state, there is an imbalance between the free radicals and the antioxidant enzymes, thus instilling oxidative stress and by extension cellular alterations on such system. [23] Adansonia digitata and Corchorous olitorius increased systemic antioxidant enzymes activities in irradiated rats [34] . Ethanol extract of Vernonia amygdalina increased the antioxidant enzymes activities of rats administered with castor oil. [19] Contained in these plants are bioactive constituents like polyphenols, flavonoids and alkaloids. [31] They have been implicated in the activation of Nrf-2 and inactivation of Nf-kB in rats exposed to irradiation. [32] In the present study, catechin, epicatechin and quercetin are polyphenols and flavonoids are responsible for the activation of Nrf-2 and inactivation of Nf-kB of irradiated rats as shown in figure 1 and 2 above. Activation of Nrf-2 have been associated with an increased antioxidant enzymes activities [19] In the present study an increased Nrf-2 activation as shown in figure 1 with a corresponding increased antioxidant enzymes activities as shown in Table 3 is suggesting that the activated Nrf-2 have bind to the antioxidant responsive element on of the DNA, thus expressing for antioxidant enzymes and other detoxifying enzymes, which are available to scavenge free radicals and stabilizes reactive intermediate generated by irradiation. [30] Conclusion From the result obtained from this research, it can there be concluded that catechin, epicatechin and quercetin can be used as oral remedy as well as nutraceuticals in the treatment of radiation-induced alteration on the cellular system. Declarations Ethical Approval Ethical approval was obtained from the University of Ilorin Ethical Committee, University of Ilorin. With the ethical approval number obtained as follow UERC/ASN/2018/1409 on the 13 th September, 2022. The study was conducted following the guidelines on the care and use of laboratory animals. Consent to Participate All authors agreed to participate from the onset of the study to the end Consent to Publish All authors agreed to published this manuscript in Journal of applied Biochemistry and Biotechnology Authors Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by BELLO, Olamilekan Kabir, SHIPEBI, Omotayo Henrietta, LUKMAN, Samiatu and SAMUEL, Joseph Asuku . The first draft of the manuscript was written by BELLO, Olamilekan Kabir and proof-read by Salawu Musa Oyewole. Funding The research was self-funded Competing Interest There are no conflict and competing interest among the authors and none with any organization. The research is self-funded. Availability of Data and Materials The Data and Materials used are available and will be presented when requested for References Jaramillo M.C., Zhang D.D. (2013). The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Dev; 27:2179–2191. Taguchi K., Yamamoto M. (2017). The KEAP1-NRF2 System in Cancer. Front. Oncol. 7:85. Canning P., Sorrell F.J., Bullock A.N. (2015). Structural basis of Keap1 interactions with Nrf2. Free Radic. Biol. Med. 88:101–107. McMahon M., Thomas N., Itoh K., Yamamoto M., Hayes J.D. (2004). 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Journal of Toxicology and Applied Pharmacology . 244:57–65. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editor assigned by journal 07 Jun, 2024 Submission checks completed at journal 07 Jun, 2024 First submitted to journal 06 Jun, 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4541075","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":311737143,"identity":"47caca35-3b18-447b-bea3-9ae1bd1544f2","order_by":0,"name":"Olamilekan Kabir BELLO","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYBACCQYGNgjFzNhw4AMDQwIJWtibDx6cQYIWIOA5lnyYhxgtku1nnz34ucNCzlwix+CwbZtdHj97A+OHjzm4tUjzpJsb9p6RMLacAdSS25ZcLNlzgFly5jbcWuQY0tgkeNskEjfcAGthBjIS2Jh58Wnhf8Ym+RemxbKtnrAWaYk0NmmwLWeOJRxmbDtMWIvkjGfsxrJtEsYGx5sPHOw5dzxxZs/BZrx+kTifxvbwbVudnMFhxuYPP8qqE/uBEfThIx4tqIARHEeMDcSqB4E/pCgeBaNgFIyCkQIAw+VUraPc4JEAAAAASUVORK5CYII=","orcid":"","institution":"University of Ilorin","correspondingAuthor":true,"prefix":"","firstName":"Olamilekan","middleName":"Kabir","lastName":"BELLO","suffix":""},{"id":311737144,"identity":"96730896-0dea-453f-8d40-a630f2d64aeb","order_by":1,"name":"Musa Oyewole Salawu","email":"","orcid":"","institution":"University of Ilorin","correspondingAuthor":false,"prefix":"","firstName":"Musa","middleName":"Oyewole","lastName":"Salawu","suffix":""},{"id":311737145,"identity":"00ac01c2-e46b-483b-9b6a-bd821ef9572b","order_by":2,"name":"Joseph Asuku Samuel","email":"","orcid":"","institution":"University of Ilorin","correspondingAuthor":false,"prefix":"","firstName":"Joseph","middleName":"Asuku","lastName":"Samuel","suffix":""},{"id":311737146,"identity":"1ea4466e-175f-4350-a37b-81d531e6b22a","order_by":3,"name":"Omotayo Henrietta","email":"","orcid":"","institution":"University of Ilorin","correspondingAuthor":false,"prefix":"","firstName":"Omotayo","middleName":"","lastName":"Henrietta","suffix":""},{"id":311737147,"identity":"6e530780-c95c-4302-aa28-eb6f1b962942","order_by":4,"name":"LUKMAN Samiatu","email":"","orcid":"","institution":"University of Ilorin","correspondingAuthor":false,"prefix":"","firstName":"LUKMAN","middleName":"","lastName":"Samiatu","suffix":""}],"badges":[],"createdAt":"2024-06-06 14:29:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4541075/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4541075/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58809262,"identity":"86d4ca7f-9bec-46b3-b3bb-85a514daa068","added_by":"auto","created_at":"2024-06-21 11:33:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":13069,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe effects of catechin, epicatechin and quercetin on the Nf-kB concentration of rats exposed to 6 grey gamma irradiation.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eValues are expressed as Means ± SEM; n=6 at (P\u0026lt;0.05); Values with same superscript are not significantly different, whereas those with different superscript are significantly different from each other\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4541075/v1/bd825ff155cda31237d67301.png"},{"id":58809263,"identity":"65134da2-5b0f-49ba-b1b9-93e9bbf8faf3","added_by":"auto","created_at":"2024-06-21 11:33:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":15522,"visible":true,"origin":"","legend":"\u003cp\u003eThe effects of catechin, epicatechin and quercetin on the Nf-kB concentration of rats exposed to 6 grey gamma irradiation.\u003c/p\u003e\n\u003cp\u003eValues are expressed as Means ± SEM; n=6 at (P\u0026lt;0.05); Values with same superscript are not significantly different, whereas those with different superscript are significantly different from each other.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4541075/v1/4382ac0d407f28d9389c3ca3.png"},{"id":58809913,"identity":"a5fe3185-0794-439d-bf7a-7c306ba6a979","added_by":"auto","created_at":"2024-06-21 11:41:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":706036,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4541075/v1/787dc1e1-5aa0-4841-95ba-259649286c95.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Catechin, Epicatechin and Quercetin against Gamma-irradiation- induced Nrf-2, Nf-kB and Antioxidant Enzymes alterations in Cellular System of Rats","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe transcription factor Nf-kB serves as a pivotal mediator of inflammatory responses.\u003csup\u003e\u0026nbsp;[26]\u003c/sup\u003e The switch-on of Nf-kB by free radicals induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokine and also participates in inflammasome regulation. \u003csup\u003e[22]\u003c/sup\u003e Consequently, deregulated Nf-kB activation contributes to various inflammatory diseases.\u003csup\u003e\u0026nbsp;[24]\u0026nbsp;\u003c/sup\u003eReactive oxygen and nitrogen species (ROS/RNS) have been implicated in the activation of Nf-kB.\u003csup\u003e\u0026nbsp;[18]\u0026nbsp;\u003c/sup\u003eAn exacerbated free radical level have been suggested to mediate an increased ROS/RNS in rats. An ROS/RNS level mediated the activation of inhibitory kappa-B kinase (ikk). ikk phosphorylate the Inhibitory kappa-B (ikB) component of the Nf-kB (the ikB is the repressor of Nf-kB in the cytosol), thus tag it for ubiquitination by the 26-s proteasome. Ubiquitination cleaved off the ikB component of Nf-kB to become active. \u003csup\u003e[21]\u003c/sup\u003e Activated Nf-kB is translocated to the nucleus where it bind the DNA binding region of the nucleus to express for inflammatory biomarkers such as cytokines, chemokine, prostaglandins etc. \u003csup\u003e[19]\u003c/sup\u003e All the expressed biomarkers are capable of causing cellular alterations in human system. \u003csup\u003e[19]\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eWhen Nf-kB is switched-off, there is possibility of having Nrf-2 switched-on. \u003csup\u003e[14]\u003c/sup\u003e Nuclear factor erythroid 2-related factor 2 (NrF-2) is a transcription factor that regulates the cellular defense against toxic and oxidative insults as well as defense against the synthesis of possible inflammatory biomarkers, usually through the expression of genes involved in oxidative stress response and drug detoxification. Nrf-2 activation renders cells resistant to chemical carcinogens and inflammatory challenges mediated by Nf-kB.\u003csup\u003e\u0026nbsp;[12]\u0026nbsp;\u003c/sup\u003eIncreased consumption of natural products such as vegetables, fruits and many other non-toxic plant substances have been implicated in the activation of a cytosolically repressed (inactive) Nrf-2. \u003csup\u003e[26]\u003c/sup\u003e Contain in these natural plant materials are bioactive constituents like polyphenols, flavonoids, catechin, quercetin, tocopherol, epicatechin, luteolin and many more. They activate inactive Nrf-2 by mediating the phosphorylation of the keap-1(cytosolic repressor of Nrf-2). This phosphorylation tagged Nrf-2 for ubiquitination by the 26-s proteasome. \u003csup\u003e[26]\u003c/sup\u003e Ubiquitination eventually cleaved-off keap-1 from Nrf-2, to become an active Nrf-2. It translocate into the nucleus where it binds to the antioxidant responsive element (ARE) region of the DNA and thus expressed for antioxidant enzymes, phase-2 enzymes and anti-inflammatory proteins. \u003csup\u003e[24]\u003c/sup\u003e These proteins/enzymes are capable of defending the cell against pro and inflammatory insult as well as oxidative insult by ROS/RNS.\u003csup\u003e\u0026nbsp;[23]\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eIncreased ROS/RNS have been implicated in antioxidant enzymes depletion.\u003csup\u003e\u0026nbsp;[28]\u003c/sup\u003e Hence an imbalance between ROS/RNS and the systemic antioxidant capacity is the underlying genesis of cellular alterations. \u003csup\u003e[25]\u0026nbsp;\u003c/sup\u003eNrf-2 have been directly linked with the expression of antioxidant enzymes, such that the higher the Nrf-2 activated, the more the antioxidant expressed, hence the more they are available to scavenge free radicals in cellular system. \u003csup\u003e[26]\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSeveral scientific studies have validated the pathological implications of an activated Nf-kB mediated by an increased free radicals, ROS and RNS in experimental rats. Scientific claims have also validated the pharmacological advantages of activating Nrf-2 through the feeding/administration of plant materials experimental rat. \u003csup\u003e[31]\u0026nbsp;\u003c/sup\u003eHave validated the solvent fractions of methanol leaves extracts of \u003cem\u003eAdansonia digitata\u003c/em\u003e and \u003cem\u003eCorchorus olitorius\u0026nbsp;\u003c/em\u003ein gamma-irradiation-induced Nf-kB, Nrf-2 and antioxidant alterations in Rats. Another studies by \u003csup\u003e[32]\u0026nbsp;\u003c/sup\u003ehave validated the amelioration of radiation-induced cellular alterations in rat administered with solvent fractions of methanol leaf extracts of \u003cem\u003eAdansonia digitata\u003c/em\u003e and \u003cem\u003eCorchorus olitorius.\u0026nbsp;\u003c/em\u003eThese research work have established the influence of plant materials on the activation and inactivation of Nrf-2 and Nf-kB as well as how they altered cellular alterations. The work by \u003csup\u003e[33]\u0026nbsp;\u003c/sup\u003ehave established the several\u003csup\u003e\u0026nbsp;\u003c/sup\u003ebioactive constituents of n-butanol subfractions of \u003cem\u003eAdansonia digitata\u003c/em\u003e and \u003cem\u003eCorchorus olitorius\u003c/em\u003e. Some of the bioactive constituents are catechin, epicatechin, luteolin, quercetin, astragalin etc. \u003csup\u003e[33]\u003c/sup\u003e However, the gap that is begging for attention is to successfully administered these bioactive constituents in these plants against irradiation-induced Nf-kB and Nrf-2 cellular alterations in rats. Hence this study aim to investigate the effect of catechin, epicatechin and quercetin against gamma-irradiation-induced Nf-kB and Nrf-2 alterations in cellular system of rats.\u003c/p\u003e"},{"header":"Materials and Method","content":"\u003cp\u003e\u003cstrong\u003e3.1 Experimental Animal\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of thirty (30), Wistar rats (200 \u0026plusmn; 5.00 g) were obtained from the Animal Holding Unit of the Department of Biochemistry, University of Ilorin, Ilorin, Nigeria. The rats were housed in clean cages and well-ventilated house conditions (Temperature: 28.30\u0026ordm;C), (Photo-period; 12hr light, 12hr dark), (Humidity: 45-55%). They were fed with pelletized rats feed (Vital Feed, Grand Cereals, Jos, Nigeria) and clean tap water which were provided before and during administration. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Exposure of Rats to Radiation and Induction of Cellular Alteration in Rats\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eExperimental rats were exposed to single dose of 6 grey whole-body gamma radiation by the method described by \u003csup\u003e[28]\u003c/sup\u003e and modified by.\u003csup\u003e\u0026nbsp;[34]\u003c/sup\u003e The rats were kept in an improvised carton cage with holes made round the carton for ventilation (carton was used to restricts the movement and ensure uniform exposure of the rats to radiation) instead of the usual radiation exposure coat that was used by. \u003csup\u003e[28]\u003c/sup\u003e\u003cstrong\u003e\u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ch5\u003e3.3 Drugs, Chemicals and Assay Kits \u0026nbsp;\u003c/h5\u003e\n\u003cp\u003eNuclear Factor Kappa-B (Nf-kB) and nuclear related factor-2 (Nrf-2) enzyme linked immunoassay (ELISA) kits were products of Cayman Laboratory Limited, United State of America (USA). All chemicals used were all prepared in all-glass distilled water using standard procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4 Preparation Catechin, Epicatechin and Quercetin Solution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe 40 mg/kg body weight solutions of catechin, epicatechin and quercetin were prepared by the method described by \u003csup\u003e[33]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.5. Table 1: Animal groupings and Administration\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.68539325842696%\" valign=\"top\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.31460674157304%\" valign=\"top\"\u003e\n \u003cp\u003eAdministration\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.68539325842696%\" valign=\"top\"\u003e\n \u003cp\u003eGroup 1 (Positive)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.31460674157304%\" valign=\"top\"\u003e\n \u003cp\u003eNon-irradiated (NIR)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.68539325842696%\" valign=\"top\"\u003e\n \u003cp\u003eGroup 2 (Negative)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.31460674157304%\" valign=\"top\"\u003e\n \u003cp\u003eIrradiated (IR)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.68539325842696%\" valign=\"top\"\u003e\n \u003cp\u003eGroup 3 \u0026nbsp;(IR +CAT)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.31460674157304%\" valign=\"top\"\u003e\n \u003cp\u003eIR + \u0026nbsp; \u0026nbsp; 40 mg/kg bwt Catechin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.68539325842696%\" valign=\"top\"\u003e\n \u003cp\u003eGroup 4 (IR + EPC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.31460674157304%\" valign=\"top\"\u003e\n \u003cp\u003eIR + 40 mg/kg bwt Epicatechin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.68539325842696%\" valign=\"top\"\u003e\n \u003cp\u003eGroup 5 (IR + QCT)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.31460674157304%\" valign=\"top\"\u003e\n \u003cp\u003eIR + 40 mg/kg bwt Quercetin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch4\u003e\u003cstrong\u003e3.6\u003c/strong\u003e .\u003cstrong\u003eAnimal sacrifice and nuclear extract preparation\u0026nbsp;\u003c/strong\u003e\u003c/h4\u003e\n\u003cp\u003eThe rats in Table 1 were sacrificed by cervical dislocation, they were dissected and tissue (liver) were isolated. The 1.14 % KCL washing solution was used to rinse the liver off blood and other stains. About 1 g of the liver were homogenized in ice cold 0.25 M sucrose solution. The homogenate were cold-centrifuged at 12000 rpm. The supernatant were discarded and sediment were retained for the preparation of nuclear extract.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.7 Preparation of nuclear extract\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe nuclear extract (from which Nf-kB and Nrf-2 were produced) was prepared by the method described by \u003csup\u003e[31]\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003e\u003cstrong\u003e3.8\u003c/strong\u003e \u003cstrong\u003eDetermination of Nf-kB and Nrf-2 Status of Irradiated Rats administered with Catechin, epicatechin and quercetin\u003c/strong\u003e\u003c/h4\u003e\n\u003ch4\u003e\u0026nbsp;Nf-kB and Nrf-2 status were described by the method adopted by\u003csup\u003e\u0026nbsp;[35]\u003c/sup\u003e\u003c/h4\u003e\n\u003cp\u003e\u003cstrong\u003e3.9. Table 2: Determination of the Antioxidant Enzymes Activities of Irradiated Rats, administered CAT, EPC and QCT\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"642\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.38317757009346%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eAntioxidant Enzymes\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"62.61682242990654%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Procedures\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.38317757009346%\" valign=\"top\"\u003e\n \u003cp\u003eSuperoxide Dismutase (SOD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"62.61682242990654%\" valign=\"top\"\u003e\n \u003cp\u003eAccording to method adopted by Haliwell \u003cem\u003eet al\u003c/em\u003e. (2021)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.38317757009346%\" valign=\"top\"\u003e\n \u003cp\u003eCatalase (CAT)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"62.61682242990654%\" valign=\"top\"\u003e\n \u003cp\u003eAccording to method adopted by Yhong-sur (1989)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.38317757009346%\" valign=\"top\"\u003e\n \u003cp\u003eGlutathione Transferase (GST)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"62.61682242990654%\" valign=\"top\"\u003e\n \u003cp\u003eAccording to method adopted by Abolaji (2015)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.38317757009346%\" valign=\"top\"\u003e\n \u003cp\u003eGlutathione Peroxidase (GPx)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"62.61682242990654%\" valign=\"top\"\u003e\n \u003cp\u003eAccording to method adopted by Lazekhs \u003cem\u003eet al.\u0026nbsp;\u003c/em\u003e(1982b)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.38317757009346%\" valign=\"top\"\u003e\n \u003cp\u003eMalondialdehyde (MDA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"62.61682242990654%\" valign=\"top\"\u003e\n \u003cp\u003eAccording to method adopted by Rice \u0026ndash;Evans \u003cem\u003eet al\u003c/em\u003e. (1986)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch4\u003e\u003cstrong\u003e3.9.1 Ethical Approval\u003c/strong\u003e\u003c/h4\u003e\n\u003cp\u003eEthical approval was obtained from the University of Ilorin Ethical Committee, University of Ilorin. With the ethical approval number obtained as follow UERC/ASN/2018/1409 on the 13\u003csup\u003eth\u003c/sup\u003e September, 2022. The study was conducted following the guidelines on the care and use of laboratory animals.\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003e\u003cstrong\u003e3.9\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp;Statistical Analysis\u0026nbsp;\u003c/strong\u003e\u003c/h4\u003e\n\u003cp\u003e\u0026nbsp;Data were expressed as mean \u0026plusmn; SEM of 6 determinations except otherwise stated. All results were statistically analyzed using Duncan Multiple Range Test and complemented with Student\u0026rsquo;s t-test. Statistical Package for Social Sciences, version 21 (SPSS Inc., Chicago, IL, USA) were used for statistical analyses. Statistical significance was set at 95% confidence interval (Mahajan, 1997).\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e4.1 The effects of catechin, epicatechin and quercetin on Nf-kB Concentration of \u0026nbsp; \u0026nbsp; \u0026nbsp;irradiated Rats\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e6 grey gamma irradiation have significantly (p\u0026lt;0.05) increased the concentration of Nf-kB in irradiated rats. Administration of catechin, epicatechin and quercetin have significantly (p\u0026lt;0.05) attenuate the level to that which favorably competed with the positive control. The competition was 100 % as shown in figure 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.2 The effects of catechin, epicatechin and quercetin on Nrf-2 Concentration of \u0026nbsp; \u0026nbsp; irradiated Rats\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e6 grey gamma irradiation have significantly (p\u0026lt;0.05) increased the concentration of Nf-kB in irradiated rats. Administration of catechin, epicatechin and quercetin have significantly (p\u0026lt;0.05) attenuate the level to that which favorably competed with the positive control. The competition was 100 % as shown in figure 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: The Effects of CAT, EPC and QCT on the Antioxidant Enzymes Activities of gamma irradiated Rats in\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u0026micro;\u003c/strong\u003e\u003cstrong\u003eg/ml/mg protein\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"648\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.296296296296298%\" valign=\"top\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003eSOD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003eCAT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003eGST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003eGPX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003eMDA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.296296296296298%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePositive (NIR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e16.34 \u0026plusmn; 0.54\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e21.56 \u0026plusmn; 0.54\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e64.21\u0026plusmn; 0.54\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e42.20 \u0026plusmn; 0.54\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e6.87 \u0026plusmn; 0.54\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.296296296296298%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNegative (IR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e4.65 \u0026plusmn; 0.54\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e8.90 \u0026plusmn; 0.54\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e15.88 \u0026plusmn; 0.54\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e12.21 \u0026plusmn; 0.54\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e22.98\u0026plusmn; 0.54\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.296296296296298%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIR + CAT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e19.89 \u0026plusmn; 0.64\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e22.45 \u0026plusmn; 0.14\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e71.2 \u0026plusmn; 0.54\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e40.86 \u0026plusmn; 0.54\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e5.34 \u0026plusmn; 0.54\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.296296296296298%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIR + EPC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e20.21 \u0026plusmn; 0.51\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e21.98 \u0026plusmn; 0.35\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e70.06 \u0026plusmn; 0.54\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e41.21 \u0026plusmn; 0.54\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e6.03 \u0026plusmn; 0.54\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.296296296296298%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIR + QCT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e20.22 \u0026plusmn; 0.44\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e22.21 \u0026plusmn; 0.54\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e72.02 \u0026plusmn; 0.54\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e41.21 \u0026plusmn; 0.54\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.74074074074074%\" valign=\"top\"\u003e\n \u003cp\u003e6.15 \u0026plusmn; 0.54\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eValues are expressed as Means \u0026plusmn; SEM; n=6 at (P\u0026lt;0.05); Values with same superscript are not significantly different, whereas those with different superscript are significantly different from each other.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cstrong\u003e\u003csup\u003e[34]\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003ehave scientifically validated, that gamma radiation induced cellular alterations by increasing Nf-kB and reducing Nrf-2 concentration to a level that is capable of causing overexpression of pro and inflammatory biomarkers such as chemokines, cytokines prostaglandins as well as increasing the generation of ROS/RNS in irradiated rats. \u003csup\u003e[24][19][34]\u003c/sup\u003e. In the present study, the increased Nf-kB and decreased Nrf-2 concentration of irradiated rats as shown in Figure \u0026nbsp;1 and 2, have been associated with the 6 grey gamma irradiation, thus, leading to a depleted antioxidant enzymes activities in the irradiated rats.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e[32]\u0026nbsp;\u003c/sup\u003eHave scientifically established that n-butanol fraction of \u003cem\u003eAdansonia digitata\u003c/em\u003e and \u003cem\u003eCorchorous olitorous\u003c/em\u003e leaves is the most effective of the three fractions (n-hexane, ethylacetate and n-butanol fractions) tested against gamma irradiation-induced Nf-kB and Nrf-2 alterations in the cellular system of rats. \u003csup\u003e[33]\u003c/sup\u003e have also validated that the n-butanol subfractions 1 and 4 of \u003cem\u003eAdansonia digitata\u0026nbsp;\u003c/em\u003eand 2 and 3 of \u003cem\u003eCorchorous olitorous\u0026nbsp;\u003c/em\u003eare the most effective of the n-butanol subfractions against gamma irradiation-induced Nf-kB and Nrf-2 alterations in rats. The high performance liquid chromatography (HPLC) fingerprinting of the n-butanol subfractions 1 and 4 of \u003cem\u003eAdansonia digitata\u0026nbsp;\u003c/em\u003eand 2 and 3 \u003cem\u003eCorchorous olitorous\u003c/em\u003e leaves revealed the presence of catechin, epicatechin, quercetin, astragalin, luteolin, eleagnin and polyunsaturated fatty acids. \u003csup\u003e[32]\u003c/sup\u003e These constituents in \u003cem\u003eAdansonia digitata\u003c/em\u003e and \u003cem\u003eCorchorous olitorous\u003c/em\u003e leaves maybe be responsible for their pharmacological action. In the present study, the groups of rats administered with CAT, EPC and QCT have significant (p\u0026lt;0.05) reduction in the level of Nf-kB and a corresponding significant increase in Nrf-2, suggesting that the CAT, EPC and QCT were able to restore the alteration in the irradiated rats system as shown in Figure 1 and 2 above. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIrradiation induced free radical generation and by extension ROS/RNS. Increased free radical from a subtoxic to toxic level will overwhelmed the systemic antioxidant enzymes capacity to a level that eventually stressed the cell. During this state, there is an imbalance between the free radicals and the antioxidant enzymes, thus instilling oxidative stress and by extension cellular alterations on such system.\u003csup\u003e\u0026nbsp;[23]\u0026nbsp;\u003c/sup\u003e\u003cem\u003eAdansonia digitata\u003c/em\u003e and \u003cem\u003eCorchorous olitorius\u003c/em\u003e increased systemic antioxidant enzymes activities in irradiated rats \u003csup\u003e[34]\u003c/sup\u003e. Ethanol extract of \u003cem\u003eVernonia amygdalina\u003c/em\u003e increased the antioxidant enzymes activities of rats administered with castor oil. \u003csup\u003e[19]\u003c/sup\u003e Contained in these plants are bioactive constituents like polyphenols, flavonoids and alkaloids.\u003csup\u003e[31]\u003c/sup\u003e They have been implicated in the activation of Nrf-2 and inactivation of Nf-kB in rats exposed to irradiation. \u003csup\u003e[32]\u003c/sup\u003e In the present study, catechin, epicatechin and quercetin are polyphenols and flavonoids are responsible for the activation of Nrf-2 and inactivation of Nf-kB of irradiated rats as shown in figure 1 and 2 above. Activation of Nrf-2 have been associated with an increased antioxidant enzymes activities\u003csup\u003e\u0026nbsp;[19]\u003c/sup\u003e In the present study an increased Nrf-2 activation as shown in figure 1 with a corresponding increased antioxidant enzymes activities as shown in Table 3 is suggesting that the activated Nrf-2 have bind to the antioxidant responsive element on of the DNA, thus expressing for antioxidant enzymes and other detoxifying enzymes, which are available to scavenge free radicals and stabilizes reactive intermediate generated by irradiation. \u003csup\u003e[30]\u003c/sup\u003e\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eFrom the result obtained from this research, it can there be concluded that catechin, epicatechin and quercetin can be used as oral remedy as well as nutraceuticals in the treatment of radiation-induced alteration on the cellular system.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was obtained from the University of Ilorin Ethical Committee, University of Ilorin. With the ethical approval number obtained as follow UERC/ASN/2018/1409 on the 13\u003csup\u003eth\u003c/sup\u003e September, 2022. The study was conducted following the guidelines on the care and use of laboratory animals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors agreed to participate from the onset of the study to the end\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors agreed to published this manuscript in Journal of applied Biochemistry and Biotechnology\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003eauthors contributed to the study conception and design. Material preparation, data collection and analysis were performed by BELLO, Olamilekan Kabir,\u0026nbsp;\u003c/em\u003eSHIPEBI, Omotayo Henrietta, LUKMAN, Samiatu and SAMUEL, Joseph Asuku\u003cem\u003e. The first draft of the manuscript was written by BELLO, Olamilekan Kabir and proof-read by Salawu Musa Oyewole.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research was self-funded\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no conflict and competing interest among the authors and none with any organization. The research is self-funded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Data and Materials used are available and will be presented when requested for\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eJaramillo M.C., Zhang D.D. (2013). The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Dev; 27:2179\u0026ndash;2191.\u003c/li\u003e\n \u003cli\u003eTaguchi K., Yamamoto M. (2017). The KEAP1-NRF2 System in Cancer. Front. Oncol. 7:85.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCanning P., Sorrell F.J., Bullock A.N. (2015). Structural basis of Keap1 interactions with Nrf2. \u003cem\u003eFree Radic. Biol. Med.\u0026nbsp;\u003c/em\u003e88:101\u0026ndash;107.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMcMahon M., Thomas N., Itoh K., Yamamoto M., Hayes J.D. (2004). 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Yakubu (2023).\u0026nbsp;Bioactive constituents of n-butanol subfractions of \u003cem\u003eAdansonia digitata\u003c/em\u003e and \u003cem\u003eCorchorus olitorius\u003c/em\u003e against gamma-irradiation-induced hepatic damage, lipid profile and antioxidant alterations in rats.\u0026nbsp;\u003cstrong\u003e\u003cem\u003eFood Chemistry Advances.\u003c/em\u003e\u003c/strong\u003e 4(2024)\u003c/li\u003e\n \u003cli\u003eNwozo, S. O. and Bello, O.K.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e(2015): Hepatoprotective and antioxidant activities of the separate and combined administration of Methanolic extract of \u003cem\u003eAdasonia digitata\u0026nbsp;\u003c/em\u003eand \u003cem\u003eCochorous olitorious\u0026nbsp;\u003c/em\u003eleaves on rats. \u003cem\u003eIlorin Journal of Science\u003c/em\u003e, 2(1): 241\u0026ndash;261.\u003c/li\u003e\n \u003cli\u003eCayman H.Y\u003cem\u003e.,\u0026nbsp;\u003c/em\u003eKlaassen, C.D., Reisman, S.A. (2010): Nrf-2 the \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;rescue \u0026nbsp;effects \u0026nbsp;of the antioxidative/electrophilic response on the liver. Journal of \u003cem\u003eToxicology and Applied Pharmacology\u003c/em\u003e. 244:57\u0026ndash;65.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"molecular-biology-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mole","sideBox":"Learn more about [Molecular Biology Reports](https://www.springer.com/journal/11033)","snPcode":"11033","submissionUrl":"https://submission.nature.com/new-submission/11033/3","title":"Molecular Biology Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Nf-kB, Nrf-2, quercetin, catechin, epicatechin, irradiation, alteration, antioxidant enzymes","lastPublishedDoi":"10.21203/rs.3.rs-4541075/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4541075/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Cell are prone to oxidative insults that are mediated by Rats exposure to gamma (γ) irradiation. These insult are nuclear factor kappa-B (Nf-kB) mediated, but the activation of nuclear related factor-2 (Nrf-2) renders cells resistant to oxidative insult and inflammatory challenges, mediated by Nf-kB. Plant materials have been used successfully to restore cellular alterations mediated by Nf-kB. Contain in these plants are catechin, epicatechin, astragalin and quercetin. Hence this study investigated the effects of catechin, epicatechin and quercetin against γ-irradiation-induced Nrf-2, Nf-kB and antioxidant enzymes alterations in Rats.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Method: \u003c/strong\u003eA total of thirty (30) rats (200 ± 5g) were distributed into 5 groups of 6 each. Except group 1, all other groups were exposed to 6 grey γ-irradiation. Group 2 were fed with rat chow and water only such that groups 3, 4 and 5 were administered catechin (CAT), epicatechin (EPC) and quercetin (QCT) at 40 mg/kg body weight respectively. The rats were sacrificed and biochemical parameters were assayed. Data were analyzed using SPSS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eIrradiation significantly (p\u0026lt;0.05) increased Nf-kB, reduced antioxidant enzymes activities, with a significant (p\u0026lt;0.05) decreased in Nrf-2 concentration of irradiated rats. Administration of CAT, EPC and QCT significantly (p\u0026lt;0.05) decreased Nf-kB and a corresponding significant (p\u0026lt;0.05) increased in Nrf-2 concentration and antioxidant enzymes activities of administered groups when compared with control.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eCAT, EPC and QCT have restored cellular alterations caused by γ-irradiation, hence can be used as protection against irradiation-induced alterations.\u003c/p\u003e","manuscriptTitle":"Catechin, Epicatechin and Quercetin against Gamma-irradiation- induced Nrf-2, Nf-kB and Antioxidant Enzymes alterations in Cellular System of Rats","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-21 11:33:03","doi":"10.21203/rs.3.rs-4541075/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorAssigned","content":"","date":"2024-06-07T10:37:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-07T10:28:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"Molecular Biology Reports","date":"2024-06-06T14:27:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"molecular-biology-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mole","sideBox":"Learn more about [Molecular Biology Reports](https://www.springer.com/journal/11033)","snPcode":"11033","submissionUrl":"https://submission.nature.com/new-submission/11033/3","title":"Molecular Biology Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"9435447e-af9a-4ac6-91ce-17e161639659","owner":[],"postedDate":"June 21st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-06-21T11:33:03+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-21 11:33:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4541075","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4541075","identity":"rs-4541075","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}