Effect of alpha-tocopherol on doxorubicin-induced changes in rat liver and heart microsomes

Rats were treated with doxorubicin (2.5 mg/kg body wt, iv) once a week for 8 weeks. Alpha-Tocopherol (400 mg/kg body wt/day) was co-administered orally for 2 months. Cytochrome-P450 (Cyt-P450) and Cytochrome-b5 (Cyt-b5) levels decreased significantly in doxorubicin treated rats. Significant decreases were observed in glucose-6-phosphatase, Cyt-P450 and Cyt-b5 reductase activities. In vitro lipid peroxidation study showed that alpha-tocopherol significantly minimises the lipid peroxide formation by doxorubicin. There was a significant change in microsomal cholesterol and phospholipid levels. Alpha-Tocopherol co-administration reduced the alterations in xenobiotic metabolising system and microsomal lipid levels. The results were discussed with reference to drug metabolising enzymes, lipid peroxidation and antioxidant nature of alpha-tocopherol.