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Antioxidant Traits and Protective Impact of Vorinostat against Cisplatin Induced Hepatoxicity in Rat

Context and Objectives: Hepatotoxicity is one of the most common side effects of cisplatin (cis diamminedichloroplatinum [II] (CDDP), the most commonly used medication in cancer chemotherapy. In low doses, vorinostat (VST) has been shown to have antioxidant and anti-inflammatory properties. The aim of this study was to see whether low dose VST could protect male Wistar rats' livers from CDDP-induced liver toxicity.


The rats were randomly divided into four groups, each with ten rats: I-control group, II-CDDP group (7.5 mg/kg I.P. single dose 5 days before the end of the experiment), III-VST group (15 mg/kg/day by gastric gavage for 28 days), and IV-CDDP + VST group (7.5 mg/kg I.P. single dose 5 days before the end of the experiment) (as in group II & III). On the 28th day, blood and liver samples were taken for biochemical and histopathological tests.


When compared to regulation, CDDP administration decreased hepatic GSH levels while increasing serum alanine transaminase, aspartate transaminase, and hepatic MDA, p53, TNF-, and NF-B levels. All unfavourable changes in these parameters were significantly reduced after pretreatment with VST. VST substantially reduced the inflammatory and degenerative changes in the liver caused by CDDP, according to histopathological research. In hepatic tissues, VST increased Bcl-2 immunoexpression while decreasing Caspas-3 immunoexpression.


Conclusion: By modulating MDA, p53, TNF-, and NF-B, VST reduces CDDP-induced hepatic toxicity in rats. It also increased Bcl-2 and decreased Caspase-3 in a significant way.


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