Betaine alleviates doxorubicin-induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2/HO?1/NLRP3 and TGF-? expression

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dc.contributor.authorPatel, Dhaneshvaree
dc.contributor.authorYadav, Poonam
dc.contributor.authorSingh, Sumeet K.
dc.contributor.authorTanwar, Sampat S.
dc.contributor.authorSehrawat, Abhishek
dc.contributor.authorKhurana, Amit
dc.contributor.authorBhatti, Jasvinder S.
dc.contributor.authorNavik, Umashanker
dc.date.accessioned2024-01-21T10:54:19Z
dc.date.accessioned2024-08-14T07:41:03Z
dc.date.available2024-01-21T10:54:19Z
dc.date.available2024-08-14T07:41:03Z
dc.date.issued2023-10-16T00:00:00
dc.description.abstractDoxorubicin (Dox) is an anthracycline antibiotic used to treat various cancers and shows severe toxicity in multiple organ systems, including kidneys. Evidence shows that betaine's antioxidant and anti-inflammatory properties could prevent the onset of several disorders. Hence, the present study aims to investigate the therapeutic potential of betaine on Dox-induced nephrotoxicity (DIN). Nephrotoxicity was induced in male Sprague Dawley rats using Dox at a dose of 4 mg/kg (cumulative dose: 20 mg/kg) by the intraperitoneal route and cotreated with betaine through oral gavage (200 and 400 mg/kg) for 28 days. At the end of the experiment, biochemical, oxidative stress parameters, histopathology, and qRT-PCR were performed. DIN was indicated by elevated serum creatinine, urea, and decreased albumin levels representing kidney damage; the histopathological lesions (increased capsular space, renal tubule damage, and fibrosis) in renal tissues supported these biochemical findings. Interestingly, betaine treatment improves these alterations in Dox-treated rats. Further, betaine treatment decreases the lipid peroxidation and nitrite concentration and increases the superoxide dismutases and catalase enzyme concentration in Dox-treated rats. Fascinatingly, at the molecular level, DIN in rats shows upregulation of the Nrf2/HO-1 gene, while betaine treatment attenuated its expression along with the downregulation of inflammatory genes (NLRP3, TLR-4, TNF-?, and IL-6) and fibrosis-related genes (TGF-? and Acta2) expression in Dox-treated rats. These results showed that betaine has reno-protective properties by reducing inflammatory and fibrotic mediators and enhancing antioxidant capacity in the renal tissue of rats treated with Dox. We believe betaine can be exploited as a dietary supplement to attenuate DIN. � 2023 Wiley Periodicals LLC.en_US
dc.identifier.doi10.1002/jbt.23559
dc.identifier.issn10956670
dc.identifier.urihttp://10.2.3.109/handle/32116/4276
dc.identifier.urlhttps://onlinelibrary.wiley.com/doi/10.1002/jbt.23559
dc.language.isoen_USen_US
dc.publisherJohn Wiley and Sons Incen_US
dc.subjectbetaineen_US
dc.subjectdoxorubicinen_US
dc.subjectfibrosisen_US
dc.subjectinflammationen_US
dc.subjectnephrotoxicityen_US
dc.subjectoxidative stressen_US
dc.titleBetaine alleviates doxorubicin-induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2/HO?1/NLRP3 and TGF-? expressionen_US
dc.title.journalJournal of Biochemical and Molecular Toxicologyen_US
dc.typeArticleen_US
dc.type.accesstypeClosed Accessen_US

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