Therapeutic effects of atorvastatin on doxorubicin‐induced hepatotoxicity in rats via antioxidative damage, anti‐inflammatory, and anti‐lipotoxicity

Abstract

AbstractDoxorubicin (DOX), is a high efficiency anthracycline antitumor drug. However, the clinical application of DOX is limited mainly by dose‐related adverse drug reactions. Currently, the therapeutic effects of Atorvastatin (ATO) on DOX‐induced hepatotoxicity were studied in vivo. The results indicated that DOX impaired hepatic function, as measured by an increased levels of liver weight index and serum concentrations of aspartate transaminase and alanine transaminase, as well as alteration of hepatic histology. In addition, DOX increased the serum levles of triglyceride (TG) and nonestesterified fatty acid. ATO prevented these changes. Mechanical analysis revealed that ATO restored the changes of malondialdehyde, reactive oxygen radical species, glutathione peroxidase and manganese superoxide dismutase. Additionally, ATO inhibited the increased expression levels of nuclear factor‐kappa B and interleukin 1β, hence suppressing inflammation. Meanwhile, ATO inhibited cell apoptosis by dramatically decreasing the Bax/Bcl‐2 ratio. In addition, ATO mitigated the lipidtoxicity by inhibiting the adipolysis of TG and accelerating hepatic lipid metabolism. Taken together, the results suggest ATO has therapeutic effect on DOX‐induced hepatotoxicity via inhibition of oxidative damage, inflammatory and apoptosis. In addition, ATO attenuates DOX‐induced hyperlipidemia via modulation of lipid metabolism.