Abstract
Background and Aim:
Cisplatin (cis-diamminedichloroplatinum [II]; CDDP) is the
most widely used drug in cancer chemotherapy. The nephrotoxicity of CDDP is one of its major
side effects. Vorinostat (VST) has been reported to have antioxidant and anti-inflammatory effects
in bothin-vitro and in vivo models. The present study aimed to explore the potential protective effects
of VST against CDDP-induced nephrotoxicity in rats.
Materials and Methods:
The rats were randomly divided into 4 groups; control group, CDDP
group (received CDDP 7.5 mg/kg IP single dose 5 days before the end of the experiment), VST
group, (received VST 15 mg/kg/day by gastric gavage for 28 days), and CDDP + VST group (received
CDDP + VST as above). Blood and kidney samples were collected on the 28th day for biochemical
and histopathological examinations.
Results :
Administration of CDDP single dose (7.5 mg/kg IP) 5 days before the end of the experiment
(at day 23) produced a significant decrease in renal glutathione levels and a significant increase
in serum urea nitrogen, creatinine, renal malondialdehyde, tumor necrosis factor-alpha, tumor
suppressor protein (p53) and nuclear factor kappa B levels compared to the control group. Pretreatment
with VST for 28 days significantly attenuated all unfavorable changes of these parameters.
Histopathological analysis showed that VST significantly decreased kidney inflammatory and
degenerative changes induced by CDDP. VST also significantly increased Bcl-2 and decreased Caspas-
3 immunoexpression in renal tissues.
Conclusion:
These results suggest that VST alleviates CDDP-induced nephrotoxicity in rats
showing a novel therapeutic potential for the management of nephrotoxicity induced by CDDP.