Abstract
Doxorubicin (DOX) is one of the most efficient anticancer chemotherapeutic drugs. However, its use is limited due to the induction of irreversible dilated cardiomyopathy and hepatotoxicity. The present study aimed to evaluate the hepatoprotective effect of trehalose (TRE) against DOX –induced cardiomyopathy(DIC). Mice were divided into five treated groups: Control group given saline, DOX group (2mg/kg body weight three times per week for three weeks day after day), TRE group (200µg/mouse three times per week for three weeks day after day), DOX+TRE cotreatment group (animals were co-administered 2mg/kg body weight of DOX with 200µg/mouse TRE by the same time), and DOX+TRE post treatment group (animals received 2mg/kg body weight DOX followed by treatment with 200µg/mouse TRE after 18 days). The obtained results indicated that DOX-treatment resulted in a decrease in body and liver weight ,and relative weight of liver compared to the control group. In addition, DOX-treatment caused an increase in activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST),and in level of hepatic malondialdehyde (MDA) concentration. However, concentration of total thiols (T-thiol), total antioxidant capacity (TAC) as well as catalase (CAT) enzyme activity were reduced in DOX-treated mice. Furthermore, dramatic changes in the histological architecture of the liver were observed. On the other hand, an improvement in the activities of ALT,AST, and CAT as well as levels of hepatic MDA ,T-thiol and TAC were observed in animals administrated with TRE either alone or in combination with DOX in cotreatment and post treatment groups in comparison with the ones treated with DOX alone. Moreover, histopathological examination of liver tissues in mice co-treated with DOX and TRE showed a significant improvement in hepatic parenchyma as compared to mice treated with DOX alone.

Key words: Doxorubicin; oxidative stress; cardiomyopathy; hepatotoxicity; trehalose.