PREVENTION OF CYCLOPHOSPHAMIDE-INDUCED DIABETES IN RATS BY CYCLOSPORINE-A

The use of cyclophosphamide, an anti-cancer and immunosuppressant drug , is accompanied by a number of side-effects. We investigated the rela tionship between cyclophosphamide-induced diabetes and increased inner membrane permeability of pancreas mitochondria. Injection of a single dose of cyclophosphamide (350 mg/kg body weight) reduced the weight o f rats and increased their blood glucose level to 8.4 +/- 0.09 mM. The ability of pancreas mitochondria of treated rats to accumulate and re tain Ca2+ and tetraphenyl phosphonium ion (TPP+) was sharply affected. Rats injected with the same dose of cyclophosphamide plus cyclosporin A (500 mu g/kg body weight) or cyclosporin A alone showed an increase in weight and a fall in blood glucose to 5.1 +/- 0.07 mM or 4.83 +/- 1 respectively. The ability of pancreas mitochondria of the same soup to accumulate and retain Ca2+ and TPP+ was restored to almost the leve l of the control group (saline-injected). These results suggested that cyclophosphamide may induce diabetes as a result of increasing the pe rmeability of pancreatic inner mitochondrial membrane. There might be relationship between the efficacy of cyclosporin A in preventing diabe tes mellitus and its protective effect on this permeability. Med Sci R es 26:447-450 (C) 1998 Lippincott-Raven Publishers.