al-Nasser I A
Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
Comp Biochem Physiol A Mol Integr Physiol. 1998 Nov;121(3):209-14. doi: 10.1016/s1095-6433(98)10135-6.
The use of Cyclophosphamide, an anti-cancer and immunosuppressant drug, is accompanied by a number of side effects. Rats injected with a single dose of cyclophosphamide (200 mg kg-1 body weight) showed an increase in the levels of serum glutamate-oxaloacetate transaminase, serum glutamate-pyruvate transaminase, glucose-6-phosphate dehydrogenase and creatine phosphokinase isoenzyme by 53, 24, 55 and 135%, respectively. Also the ability of heart or liver mitochondria to retain accumulated Ca2+ and tetraphenylphosphonium ion was sharply affected in treated rats. Rats injected with the same dose of cyclophosphamide plus cyclosporin A (500 micrograms kg-1 body weight) showed reduction in the levels of those enzymes by about 44, 21, 43 and 57%, respectively compared to cyclophosphamide-treated rats. Cyclosporin A treatment also restored mitochondrial ability to retain accumulated Ca2+ and tetraphenyl phosphonium ions nearly to the level of untreated rats. We suggest that cyclophosphamide induced cardio and hepatotoxicity by increasing heart and liver inner mitochondrial membrane permeability to Ca2+. The protective effect of cyclosporin A against cyclophosphamide-induced damage also support this suggestion.
