The effects of monobromobimane on calcium and phenylarsineoxide-induced mitochondrial swelling and cytochrome c release in isolated brain mitochondria

Abstract

A possible involvement of inhibitory effects of monobromobimane (MBM), a thiol reagent, on the swelling and the release of cytochrome c in the isolated brain mitochondria was examined. MBM dose-dependently inhibited the calcium and phenylarsineoxide-induced mitochondrial swelling and cytochrome c release. Significant relationships between mitochondrial swelling and cytochrome c release were detected. Furthermore, effects of in vivo treatment with MBM on neuronal cell damage after transient (15 min) global ischemia in rats were examined. Infusion of MBM (1 or 3 μg/animal) to cerebral ventricles attenuated an increased number of TUNEL-positive cells and neuronal cell death in the hippocampal CA1 region at 72 h of reperfusion. These results suggest that MBM may have an ability to inhibit mitochondria-associated apoptotic pathways through attenuation of the mitochondrial swelling and the release of cytochrome c. © 2004 Pharmaceutical Society of Japan.