Antioxidant Traits and Protective Impact of Vorinostat against Cisplatin Induced Hepatoxicity in Rats
Hala Salah Abdel Kawy Eweis *
Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Omnyah Mohammad Omar Bashraf
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia.
Ahmed Shaker Ali
Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Soad Shaker Ali
Department of Anatomy, Faculty of Medicine, King Abdulaziz University Jeddah, Saudi Arabia.
*Author to whom correspondence should be addressed.
Abstract
Background and Aim: Cisplatin "cis diamminedichloroplatinum [II] (CDDP) is the most widely used drug in cancer chemotherapy and hepatotoxicity is one of its major side effects. Vorinostat (VST) has been recognized to have an antioxidant and anti-inflammatory effect in low doses. The present study aimed to explore the potential protective effects of low dose VST against CDDP induced-liver toxicity in male Wistar rats.
Methods: The rats were randomly divided into 4 groups (10 rats each); 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 (as in group II & III). Blood and livers samples were collected at the day 28th for biochemical and histopathological examinations.
Results: Administration of CDDP significantly decrease hepatic GSH levels and increase serum alanine transaminase, aspartate transaminase and hepatic MDA, p53, TNF-α, and NF-κB levels compared to control. Pretreatment with VST significantly attenuated all unfavorable changes in these parameters. Histopathological analysis showed that VST significantly decreased liver inflammatory and degenerative changes induced by CDDP. VST also significantly increased Bcl-2 and decreased Caspas-3 immunoexpression in hepatic tissues.
Conclusion: VST alleviates CDDP induced hepatic toxicity in rats by modulating MDA, p53, TNF-α, and NF-κB. It also significantly increased Bcl-2 and decreased Caspase-3.
Keywords: Vorinostat, cisplatin, hepatotoxicity, GSH, malondialdehyde, tumor necrosis factor-alpha, and nuclear factor kappa B.