Apilarnil protects against the copper nanoparticle hepato-renal toxicity in rats associated with oxidative stress, inflammation, apoptosis, autophagy

Apilarnil protects against the copper nanoparticle hepato-renal toxicity in rats associated with oxidative stress, inflammation, apoptosis, autophagy | 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 Apilarnil protects against the copper nanoparticle hepato-renal toxicity in rats associated with oxidative stress, inflammation, apoptosis, autophagy Aydın GENÇ, Sefa KÜÇÜKLER, Fatih Mehmet KANDEMİR This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8796570/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 This study aimed to investigate the protective effects of apilarnil against hepatorenal damage induced by copper nanoparticles in rats. A total of 35 rats were randomly divided into five groups (n = 7): Control (physiological saline), APL (400 mg/kg apilarnil), Cu (100 mg/kg copper nanoparticles), Cu + APL 200 (100 mg/kg copper + 200 mg/kg apilarnil) and Cu + APL 400 (100 mg/kg copper + 400 mg/kg apilarnil). All treatments were administered orally by gavage for 28 days. In the copper nanoparticle-treated group, significant decreases in antioxidant enzyme activities, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT), as well as reduced glutathione (GSH) levels, were observed, accompanied by a marked increase in malondialdehyde (MDA) levels compared to the control group. Apilarnil administration significantly attenuated oxidative stress by restoring antioxidant parameters and reducing MDA levels toward control values. Copper nanoparticle exposure activated autophagy-related signaling pathways through phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT3), and mammalian target of rapamycin (mTOR). Additionally, it induced endoplasmic reticulum (ER) stress via increased expression of activating transcription factor 6 (ATF6), glucose-regulated protein 78 (GRP78), protein kinase RNA-like ER kinase (PERK), and C/EBP homologous protein (CHOP). Copper exposure also elevated inflammatory markers, including Toll-like receptor 4 (TLR4), high mobility group box-1 (HMGB-1), nuclear factor-kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α). Apilarnil treatment effectively suppressed autophagy activation, ER stress, and inflammatory responses, demonstrating pronounced antioxidant, anti-inflammatory, and antiautophagic effects. These findings suggest that apilarnil may serve as a potential alternative therapeutic agent against copper nanoparticle-induced liver and kidney toxicity. apilarnil copper nanoparticle liver and kidney damage oxidative stress Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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-8796570","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":586696920,"identity":"60a95712-63a1-4766-aed2-9c11e0735581","order_by":0,"name":"Aydın GENÇ","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYNCCigM8QJLxAAMDM7FazoC1MEC0sBGjg7HtAAPxWvj7Fx978HPeHRlz/sUHDjBUWCc2yPc+wKtF4sazdMPebc94LGc8SzjAcCY9sYGN3QC/NTfOmEkzbjvMY3DjjMEBxrbDQC0EXCZ/4/w3acY5MC3/iNBicL6HTZqxAajlfA9QSwMRWgxvsJlJ9hx7BrSFLeFAwrF04za2NPxa5M4ffibxo+aOvcH5wwcffKixlu1nPoZfC4NEAhIDxCYck/wH0BmjYBSMglEwCtAAANrBTEqk80/gAAAAAElFTkSuQmCC","orcid":"","institution":"Bingol University","correspondingAuthor":true,"prefix":"","firstName":"Aydın","middleName":"","lastName":"GENÇ","suffix":""},{"id":586696921,"identity":"ee16be31-4f64-4108-b989-fe76d67741bb","order_by":1,"name":"Sefa KÜÇÜKLER","email":"","orcid":"","institution":"Atatürk University","correspondingAuthor":false,"prefix":"","firstName":"Sefa","middleName":"","lastName":"KÜÇÜKLER","suffix":""},{"id":586696924,"identity":"931f2a25-583a-494c-93dd-4e58bf06d6ec","order_by":2,"name":"Fatih Mehmet KANDEMİR","email":"","orcid":"","institution":"Aksaray University","correspondingAuthor":false,"prefix":"","firstName":"Fatih","middleName":"Mehmet","lastName":"KANDEMİR","suffix":""}],"badges":[],"createdAt":"2026-02-05 11:54:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8796570/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8796570/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104673004,"identity":"9f64de59-6eb2-478b-a93a-37624287bf9d","added_by":"auto","created_at":"2026-03-15 20:09:30","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2252770,"visible":true,"origin":"","legend":"","description":"","filename":"Maintext.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8796570/v1_covered_fa844184-6019-4b18-bf47-69ee0342964d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Apilarnil protects against the copper nanoparticle hepato-renal toxicity in rats associated with oxidative stress, inflammation, apoptosis, autophagy","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":"apilarnil, copper nanoparticle, liver and kidney damage, oxidative stress","lastPublishedDoi":"10.21203/rs.3.rs-8796570/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8796570/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study aimed to investigate the protective effects of apilarnil against hepatorenal damage induced by copper nanoparticles in rats. A total of 35 rats were randomly divided into five groups (n\u0026thinsp;=\u0026thinsp;7): Control (physiological saline), APL (400 mg/kg apilarnil), Cu (100 mg/kg copper nanoparticles), Cu\u0026thinsp;+\u0026thinsp;APL 200 (100 mg/kg copper\u0026thinsp;+\u0026thinsp;200 mg/kg apilarnil) and Cu\u0026thinsp;+\u0026thinsp;APL 400 (100 mg/kg copper\u0026thinsp;+\u0026thinsp;400 mg/kg apilarnil). All treatments were administered orally by gavage for 28 days. In the copper nanoparticle-treated group, significant decreases in antioxidant enzyme activities, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT), as well as reduced glutathione (GSH) levels, were observed, accompanied by a marked increase in malondialdehyde (MDA) levels compared to the control group. Apilarnil administration significantly attenuated oxidative stress by restoring antioxidant parameters and reducing MDA levels toward control values. Copper nanoparticle exposure activated autophagy-related signaling pathways through phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT3), and mammalian target of rapamycin (mTOR). Additionally, it induced endoplasmic reticulum (ER) stress via increased expression of activating transcription factor 6 (ATF6), glucose-regulated protein 78 (GRP78), protein kinase RNA-like ER kinase (PERK), and C/EBP homologous protein (CHOP). Copper exposure also elevated inflammatory markers, including Toll-like receptor 4 (TLR4), high mobility group box-1 (HMGB-1), nuclear factor-kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α). Apilarnil treatment effectively suppressed autophagy activation, ER stress, and inflammatory responses, demonstrating pronounced antioxidant, anti-inflammatory, and antiautophagic effects. 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