Amelioration Of Doxorubicin-Induced Liver And Kidney Toxicities By Nicorandil Alone And Co-Administered With Prednisolone And Diltiazem

Abstract

Antineoplastic agents are widely used in cancer chemotherapy, despite causing organ toxicity. This study was conducted to investigate the ameliorative properties of nicorandil alone and co-administered with prednisolone and diltiazem on doxorubicin-induced hepato- and nephrotoxicities in rats. Seventy female Wistar rats were treated for 16 days as follows: GI: normal saline (10 ml/kg; normal control); GII: normal saline (doxorubicin control); GIII: gallic acid (200 mg/kg); GIV-VI: nicorandil (0.22, 0.43 and 0.86 mg/kg respectively); GVII: diltiazem (3.43 mg/kg); GVIII: diltiazem + nicorandil (0.43 mg/kg); IX: prednisolone (0.57 mg/kg); and GX: prednisolone + nicorandil (0.43 mg/kg). Doxorubicin (40 mg/kg) was administered on day 14 i.p. to animals in GII-X. Nicorandil significantly (p<0.05) decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST), renal creatinine, renal and hepatic malondialdehyde (MDA), and increased hepatic and renal catalase (CAT) and superoxide dismutase (SOD), compared to those administered doxorubicin alone. Co-administration of nicorandil with prednisolone and diltiazem significantly increased catalase, glutathione and superoxide dismutase, and decreased malondialdehyde, compared with the doxorubicin-only group. In conclusion, nicorandil decreased renal and hepatic markers of injury and increased enzymatic and non-enzymatic antioxidants. Co-administration with the calcium channel blocker/phospholipase A₂ inhibitor did not elicit superior protective effect.