ABSTRACT
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.
Subject(s)
Animals , Doxorubicin/pharmacology , Heart/drug effects , Male , Microsomes/drug effects , Microsomes, Liver/drug effects , Rats , Rats, Inbred Strains , Vitamin E/pharmacologyABSTRACT
The beneficial effect of alpha-tocopherol on doxorubicin-induced toxicity was studied in rats. alpha-Tocopherol (400 mg/kg/day) was administered orally, daily for a period of 2 months along with/without doxorubicin (2.5 mg/kg, i v weekly once for 8 weeks). Histology showed liver necrosis, heart myocyte degeneration, glomerular and tubular degeneration, cellular infiltration and desquammation of intestinal mucosa in doxorubicin treated animals. There was a significant increase in lipid peroxide levels measured in terms of "TBA reactants" in all these organs. These changes were associated with elevated levels of serum enzymes such as transaminases, creatine kinase and lactate dehydrogenase. The pathological observations, were minimal in animals receiving both doxorubicin and alpha-tocopherol. The lipid peroxide levels were low with concomitant normal levels of serum and intestinal enzymes in those animals.