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.
Highlights
Many drugs have been implicated in hepatotoxicity which usually results in cell death of hepatocyte [1]
Administration of cis diamminedichloroplatinum [II] (CDDP) significantly decrease hepatic GSH levels and increase serum alanine transaminase, aspartate transaminase and hepatic MDA, p53, Tumor-necrosis factor-α (TNF-α), and Nuclear factor kappa B (NF-κB) levels compared to control
Histopathological analysis showed that VST significantly decreased liver inflammatory and degenerative changes induced by CDDP
Summary
Many drugs have been implicated in hepatotoxicity which usually results in cell death of hepatocyte [1]. CDDP; induced hepatotoxic effects was manifested as an increased level of liver enzymes [5,6] It can be explained because of suppresses antioxidant defense system by increases the production of reactive oxygen species (ROS) [7]; Previous research showed that there are signs of CDDP induced liver toxicity which indicate and the acceleration of the peroxidative mechanisms in the liver cell [8]. These changes lead to a marked reduction of levels of glutathione (GSH) and increase levels of hepatic malondialdehyde (MDA) [9]. Blood and livers samples were collected at the day 28th for biochemical and histopathological examinations.
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