Protective mechanisms of atorvastatin in ameliorating doxorubicin‐induced hepato‐renal toxicity

Abstract

This study aimed to investigate the mechanisms by which the anticancer drug doxorubicin (Dox)‐induced hepato‐renal damage could be prevented by Atorvastatin(Ator), a cholesterol‐lowering statin. Ator (10 mg/kg for 10 days) was administered orally, and, in independent rat groups, Dox hepato‐renal toxicity was induced via a single i.p. dose (15 mg/kg at day 5 of experiment), with or without Ator. Dox caused deterioration in hepato‐renal function, as it increased BUN, creatinine, ALT and AST levels compared to control. Dox also caused distortion in normal renal and hepatic histology, with significant oxidative stress, as it decreased GSH concentration and catalase activity and increased malondialdehyde level. In addition, Dox caused nitrosative stress, as it increased No level, with down‐regulation of eNOS. Furthermore, Dox caused inflammatory effects as shown by up‐regulation of hepato‐renal NF‐κB expression and increment of TNF‐α concentration. Dox also caused apoptotic effect, as it up‐regulated Bax expression in liver and kidney. Using Ator with Dox restored hepato‐renal functions and histological structure, also reversed oxidative/nitrosative stress markers, inflammatory signs and apoptosis. These findings suggest Ator as a protective adjuvant against Dox toxicity, via antioxidant, anti‐nitrosative, anti‐inflammatory and anti‐apoptotic mechanisms.