Albumin replacement reduces mortality in hypoalbuminemic rats with LPS-induced endotoxemia

Albumin replacement reduces mortality in hypoalbuminemic rats with LPS-induced endotoxemia | 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 Albumin replacement reduces mortality in hypoalbuminemic rats with LPS-induced endotoxemia Hermes Vieira Barbeiro, Sérgio Catanozi, Denise Frediani Barbeiro, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5361860/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Hypoalbuminemia may influence the clinical response and mortality induced by endotoxemia. Sepsis impairs adequate tissue perfusion, and early volume resuscitation by albumin or crystalloid administration is critical for clinical outcomes and survival. Methods : This study analyzed in hypoalbuminemic rats the effects of endotoxemia on vascular reactivity, cardiac function, oxidative and inflammatory profile, and survival. In addition, mortality was accessed after albumin replacement. Endotoxemia was induced in male Sprague Dawley (SD) or Nagase analbuminemic rats (NAR) using either lipopolysaccharide (LPS) injection or cecal ligation and puncture (CLP), with or without subsequent albumin replacement. Survival rates were assessed every 8 h for 5 days following LPS injection. Hemodynamic evaluations were conducted 4 hours post-LPS injection by measuring mean arterial pressure (MAP), left ventricular end-diastolic pressure, dP/dtmax, and dP/dtmin. Vascular reactivity of aortic rings was recorded 4 hours post-LPS. Oxidative stress, measured by thiobarbituric acid reactive substances (TBARS), and cytokine levels, determined by ELISA, were assessed at 1.5 and 4 hours post-LPS injection. Comparisons among groups were performed using ANOVA with post-hoc Tukey-Kramer analysis Results : Survival rates were lower in NAR+LPS (25%) and NAR+CLP (10%) compared to SD+LPS (80%) and SD+CLP (40%), but albumin replacement improved survival in NAR+LPS (25%) as compared to NAR+LPS+ALB (55%). Severe hemodynamic impairments, including reduced cardiac function and vascular reactivity, were observed in NAR+LPS. Baseline and post-LPS plasma levels of TBARS and nitric oxide were elevated in NAR, while TNF, IL-6, and IL-10 were higher in SD+LPS compared to NAR+LPS. Discussion : Subgroup analysis of studies with volume infusion suggests that septic patients with hypoalbuminemia may benefit from albumin infusion during shock. To further investigate the role of prior hypoalbuminemia in septic shock and the underlying pathophysiological mechanisms, we conducted a translational study bridging clinical findings with experimental research. The results demonstrate that hypoalbuminemia cause alterations in endothelial and vascular muscle function as well as cardiac dysfunction. Conclusion : Hypoalbuminemia in rats increase mortality from endotoxemia, associated with severe cardiovascular dysfunction and oxidative stress. Albumin replacement in hypoalbuminemic rats reduced mortality in endotoxemia-induced sepsis. septic shock lipopolysaccharide cecal ligation puncture hypoalbuminemia albumin replacement Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Full Text Additional Declarations No competing interests reported. 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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-5361860","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":378292424,"identity":"2844c5cc-e4d8-4f02-9369-bd2c9127b253","order_by":0,"name":"Hermes Vieira Barbeiro","email":"","orcid":"","institution":"Faculdade de Medicina - Clínica Médica - Emergencias Clínicas","correspondingAuthor":false,"prefix":"","firstName":"Hermes","middleName":"Vieira","lastName":"Barbeiro","suffix":""},{"id":378292425,"identity":"69620455-d1fb-40aa-956c-aeb067da3145","order_by":1,"name":"Sérgio Catanozi","email":"","orcid":"","institution":"Faculdade de Medicina- Clínica Médica ´Endocrinologia","correspondingAuthor":false,"prefix":"","firstName":"Sérgio","middleName":"","lastName":"Catanozi","suffix":""},{"id":378292426,"identity":"b729d3b3-c3ef-4ca7-9fb2-29b67e52fcca","order_by":2,"name":"Denise Frediani Barbeiro","email":"","orcid":"","institution":"Faculdade de Medicina - Clínica Médica - Emergencias Clínicas","correspondingAuthor":false,"prefix":"","firstName":"Denise","middleName":"Frediani","lastName":"Barbeiro","suffix":""},{"id":378292427,"identity":"b4391e2c-b8f6-4216-b57e-0fb4cb47c450","order_by":3,"name":"Clara Batista Lorigados","email":"","orcid":"","institution":"Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo","correspondingAuthor":false,"prefix":"","firstName":"Clara","middleName":"Batista","lastName":"Lorigados","suffix":""},{"id":378292428,"identity":"92a93b54-5504-4462-9257-44d99f4b31a9","order_by":4,"name":"Marisa Passarelli","email":"","orcid":"","institution":"Faculdade de Medicina- Clínica Médica ´Endocrinologia","correspondingAuthor":false,"prefix":"","firstName":"Marisa","middleName":"","lastName":"Passarelli","suffix":""},{"id":378292429,"identity":"f7a0a90f-7734-4908-8889-801a562fc79e","order_by":5,"name":"Francisco Garcia Soriano","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuElEQVRIiWNgGAWjYLCCBCDmBzEYG0jRItlAkhYQMDhArBZ5/8PHPjyouSNnfCP92QPGHfcIazG8kZY8I+HYM2OzGznmBoxnionQMoPHmCGB7XDiths5bBKMbQlEaOk/A9Ty73Di5hnpz4jTIs+QY8yQ2HY4cYNEghlxWgwk0pIZEvsOG0uceWNukHiGGFv6Dx9m/PHtsBx/OzDEPu4gxpYDCDYbAxEagLY0IGsZBaNgFIyCUYANAABiHDrGT0ymTgAAAABJRU5ErkJggg==","orcid":"","institution":"Faculdade de Medicina - Clínica Médica - Emergencias Clínicas","correspondingAuthor":true,"prefix":"","firstName":"Francisco","middleName":"Garcia","lastName":"Soriano","suffix":""}],"badges":[],"createdAt":"2024-10-30 15:08:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5361860/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5361860/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":69301873,"identity":"5493b5d3-74d0-4f70-8e14-25665ef4fa22","added_by":"auto","created_at":"2024-11-19 03:05:26","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":74222,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival rate after endotoxemia. (A) Endotoxemia was induced in SD rats (n=20) and NAR (n=20) by LPS injection (10 mg/kg) and animals were observed for 48 h, and mortality was recorded every 8h. (B) In a subgroup of animals, survival was monitored in LPS-endotoxemic NAR administered with saline or albumin (n=20 per group). (C) CLP was performed in NAR to induce septic shock and survival monitored as described. Results are depicted in a Kaplan-Meyer curve analyzed by Log-Rank test (*p˂0.05).\u003c/p\u003e\n\u003cp\u003eNAR = Nagase analbuminemic rats; SD = Sprague Dawley rats; LPS = lipopolysaccharide; CLP = cecal ligation and puncture.\u003c/p\u003e","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5361860/v1/ebdf1016b0b2826d2c32659a.jpg"},{"id":69301658,"identity":"1dd4f08e-5e8e-48b5-8f59-47e08198c968","added_by":"auto","created_at":"2024-11-19 02:57:26","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":74870,"visible":true,"origin":"","legend":"\u003cp\u003eVascular reactivity after LPS-induced endotoxemia. Endotoxemia was induced in SD rats and NAR by LPS injection (10 mg/kg). Thoracic aorta was harvested after 4 h of LPS injection in NAR or SD rats to measure the aortic rings contraction to norepinephrine in the presence (A) or absence of endothelium (B) and relaxation to acetylcholine (C). Data are presented as mean ± SEM (n=6 per group) and comparisons among the maximal effect and EC50 were done by ANOVA and Tukey post-test. *p \u0026lt;0.05 NAR vs. NAR+LPS; # p\u0026lt;0.05 NAR+LPS vs. SD+LPS.\u003c/p\u003e\n\u003cp\u003eNAR = Nagase analbuminemic rats; SD = Sprague Dawley rats; LPS = lipopolysaccharide.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5361860/v1/03192de1ef62e434dd7e0c53.jpg"},{"id":69301875,"identity":"2bb0035d-7abe-4953-b338-9522d5419acc","added_by":"auto","created_at":"2024-11-19 03:05:26","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":31347,"visible":true,"origin":"","legend":"\u003cp\u003eVascular permeability after LPS-induced endotoxemia. Endotoxemia was induced in SD rats and NAR by LPS injection (10 mg/kg) and vascular permeability was determined in lung tissue after injection of Evans Blue as described in the Material and Methods section. Data are presented as mean ± SEM (n=6 per group) and comparisons were done by the Student t test.\u003c/p\u003e\n\u003cp\u003eNAR = Nagase analbuminemic rats; SD = Sprague Dawley rats; LPS = lipopolysaccharide.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5361860/v1/0a6f0fc805f32e9e48094f4f.jpg"},{"id":69303166,"identity":"2d9daded-237e-4574-858c-c010a362ebc1","added_by":"auto","created_at":"2024-11-19 03:13:26","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":49910,"visible":true,"origin":"","legend":"\u003cp\u003ePlasma lipids after LPS-induced endotoxemia. Endotoxemia was induced in SD rats and NAR by LPS injection (10 mg/kg). Plasma total cholesterol and triglycerides levels were determined before (time 0) and after LPS (1.5 h and 4 h) by enzymatic techniques. Data are presented as mean ± SEM (n=6 per group) and comparisons were done by the Student t test; *p\u0026lt;0.05.\u003c/p\u003e\n\u003cp\u003eNAR = Nagase analbuminemic rats; SD = Sprague Dawley rats; LPS = lipopolysaccharide.\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5361860/v1/e53731257681d40b4e47d863.jpg"},{"id":69301876,"identity":"4a98755d-41bc-4abc-802c-52a66169319f","added_by":"auto","created_at":"2024-11-19 03:05:26","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":57849,"visible":true,"origin":"","legend":"\u003cp\u003eSystemic oxidative stress after LPS-induced endotoxemia. Endotoxemia was induced in SD rats and NAR by LPS injection (10 mg/kg). Plasma levels of TBARS (A), plasma levels of nitrite (B), and aortic superoxide levels (C) were determined before and after 4 h of LPS injection in NAR or SD rats. Data are presented as mean ± SEM (n=8 per group) and comparisons were done by the Student t test; *p\u0026lt;0.05.\u003c/p\u003e\n\u003cp\u003eNAR = Nagase analbuminemic rats; SD = Sprague Dawley rats; LPS = lipopolysaccharide; TBARS = thiobarbituric acid reactive substances.\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5361860/v1/98f5c46c5477ff9c8256fa6f.jpg"},{"id":69301661,"identity":"862de159-7fe1-44c5-b2ce-3353a5c51662","added_by":"auto","created_at":"2024-11-19 02:57:26","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":59667,"visible":true,"origin":"","legend":"\u003cp\u003ePlasma cytokine levels after endotoxemia induction by LPS. Endotoxemia was induced in SD rats and NAR by LPS injection (10 mg/kg). Plasma levels of IL-6 (A), TNF (B), and IL-10 (C) were measured by ELISA before (0) and 1.5 h and 4 h after LPS injection. Data are presented as mean ± SEM (n=8 per group) and comparisons were done by the Student t test; *p\u0026lt;0.05.\u003c/p\u003e\n\u003cp\u003eNAR = Nagase analbuminemic rats; SD = Sprague Dawley rats; LPS = lipopolysaccharide.\u003c/p\u003e","description":"","filename":"Figure6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5361860/v1/bed584f7dc02f1d06c570369.jpg"},{"id":69303494,"identity":"83bc9136-efdd-4727-9cc5-0cbde80f10fb","added_by":"auto","created_at":"2024-11-19 03:21:27","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":888497,"visible":true,"origin":"","legend":"","description":"","filename":"PaperNAR2024.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5361860/v1_covered_4923d498-cc69-4379-961b-8297a249986a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Albumin replacement reduces mortality in hypoalbuminemic rats with LPS-induced endotoxemia","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"septic shock, lipopolysaccharide, cecal ligation puncture, hypoalbuminemia, albumin replacement","lastPublishedDoi":"10.21203/rs.3.rs-5361860/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5361860/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Hypoalbuminemia may influence the clinical response and mortality induced by endotoxemia. Sepsis impairs adequate tissue perfusion, and early volume resuscitation by albumin or crystalloid administration is critical for clinical outcomes and survival.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This study analyzed in hypoalbuminemic rats the effects of endotoxemia on vascular reactivity, cardiac function, oxidative and inflammatory profile, and survival. In addition, mortality was accessed after albumin replacement. Endotoxemia was induced in male Sprague Dawley (SD) or Nagase analbuminemic rats (NAR) using either lipopolysaccharide (LPS) injection or cecal ligation and puncture (CLP), with or without subsequent albumin replacement. Survival rates were assessed every 8 h for 5 days following LPS injection. Hemodynamic evaluations were conducted 4 hours post-LPS injection by measuring mean arterial pressure (MAP), left ventricular end-diastolic pressure, dP/dtmax, and dP/dtmin. Vascular reactivity of aortic rings was recorded 4 hours post-LPS. Oxidative stress, measured by thiobarbituric acid reactive substances (TBARS), and cytokine levels, determined by ELISA, were assessed at 1.5 and 4 hours post-LPS injection. Comparisons among groups were performed using ANOVA with post-hoc Tukey-Kramer analysis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Survival rates were lower in NAR+LPS (25%) and NAR+CLP (10%) compared to SD+LPS (80%) and SD+CLP (40%), but albumin replacement improved survival in NAR+LPS (25%) as compared to NAR+LPS+ALB (55%). Severe hemodynamic impairments, including reduced cardiac function and vascular reactivity, were observed in NAR+LPS. Baseline and post-LPS plasma levels of TBARS and nitric oxide were elevated in NAR, while TNF, IL-6, and IL-10 were higher in SD+LPS compared to NAR+LPS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e: Subgroup analysis of studies with volume infusion suggests that septic patients with hypoalbuminemia may benefit from albumin infusion during shock. To further investigate the role of prior hypoalbuminemia in septic shock and the underlying pathophysiological mechanisms, we conducted a translational study bridging clinical findings with experimental research. The results demonstrate that hypoalbuminemia cause alterations in endothelial and vascular muscle function as well as cardiac dysfunction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Hypoalbuminemia in rats increase mortality from endotoxemia, associated with severe cardiovascular dysfunction and oxidative stress. Albumin replacement in hypoalbuminemic rats reduced mortality in endotoxemia-induced sepsis.\u003c/p\u003e","manuscriptTitle":"Albumin replacement reduces mortality in hypoalbuminemic rats with LPS-induced endotoxemia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-19 02:57:21","doi":"10.21203/rs.3.rs-5361860/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e463729f-d22a-4b06-930b-38c3c6dae805","owner":[],"postedDate":"November 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-19T02:57:21+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-19 02:57:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5361860","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5361860","identity":"rs-5361860","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}