Protective effect of pravastatin on doxorubicin-induced hepatotoxicity.

OBJECTIVE: The present study was designed to investigate the possible protection of pravastatin against hepatic oxidative stress and dysfunctions induced by doxorubicin in rats.

BACKGROUND: Statins have beneficial effects on oxidative stress and inflammation.

METHODS: Male Sprague-Dawley rats were divided into four groups. Control group (received saline orally), Group 2 received pravastatin (20 mg/kg, i.p. for 15 days), Group 3 received single dose doxorubicin (15 mg/kg, i.p.), Group 4 was treated with pravastatin (20 mg/kg, i.p.) daily from 5 days before to 10 days after injection of doxorubicin (15 mg/kg, i.p.). Hepatic toxicity was estimated by biochemical parameters and oxidative stress and histopathological studies.

RESULTS: Administration of doxorubicin indicated an increase in ALT, AST, ALP, TG, cholesterol, LDL and total bilirubin levels (p < 0.01). Doxorubicin caused a reduction in HDL and albumin levels (p < 0.01) as well as superoxide dismutase, glutathione peroxidase and catalase activities (p < 0.05) with a concomitant increase in liver malondialdehyde (p < 0.05) and liver damage (p < 0.001). Pravastatin reduced the scale liver injury (p < 0.001) and protected liver functions and other biochemical parameters (p < 0.01). Increase in malondialdehyde level associated with a reduction in antioxidant activities in the doxorubicin group was attenuated by pravastatin treatment (p < 0.05).

CONCLUSION: Results indicated that pravastatin has a protective effect on the liver against doxorubicin-induced hepatotoxicity in rats (Tab. 3, Fig. 2, Ref. 34).