Hepatoprotective effect of simvastatin in mice with DMBA-induced breast cancer: Histopathological, biochemical and antioxidant status evaluation

Abstract

Introduction: This study evaluates the effects of simvastatin on the liver, in a mouse model of DMBA-induced breast cancer, with regards to histopathological, biochemical and antioxidant features. Methods: Mice were randomly divided into two groups: A (control group) and B (mammary tumor group); the latter group received DMBA (50 mg/kg) by oral gavage once a week for 4 consecutive weeks. Animals positive for breast cancer tumors were randomly divided into 3 subgroups: 1) no treatment group (D1), 2) mice that received simvastatin (80 mg/kg) per os (P.O.) daily for 4 consecutive weeks (D2), and 3) mice that received tamoxifen (50 mg/kg) P.O. daily for 4 consecutive weeks (D3). Results: Administration of simvastatin to D2 mice resulted in significantly higher superoxide dismutase (SOD) activity as well as glutathione peroxidase (GPx) activity and total antioxidant capacity (TAC), and accompanied by reduced malondialdehyde (MDA) content in liver as compared to D1 group. Tamoxifen significantly increased liver glutathione (GSH) content as compared to D1 mice. Moreover, MDA levels in liver of mice treated with tamoxifen were significantly lower than in the D1 group. Mice in the D1 group showed significantly increased levels of alkaline phosphatase (ALP), aspartate transaminase (AST), and gamma-glutamyl transferase (GGT) in liver tissues; these levels were significantly reduced by simvastatin administration. Moreover, tamoxifen decreased ALP and AST activities. Histopathological examination of liver sections from mice in the D1 group showed severe deteriorative changes. The extent and severity of changes in D2 and D3 groups were almost the same and milder than D1 group. Conclusion: In conclusion, simvastatin appears to have a hepatoprotective role in mice with DMBA-induced breast cancer, due partly to its antioxidant properties.