Mitochondrial permeability transition induced by 1-hydroxyethyl radical

Impairment of mitochondrial functions has been found in ethanol-induced liv er injury. Ethanol can be oxidized to the 1-hydroxyethyl radical (HER) by r at liver microsomal systems. Experiments were carried out to evaluate the a bility of HER to cause mitochondrial swelling as an indicator of the mitoch ondrial permeability transition (MPT). Electron spin resonance (ESR) spectr oscopy was used to detect HER and to study its interaction with mitochondri a. The ESR signal intensity of the spin adduct formed from alpha-(4-pyridyl -1-oxide) N-tert-butylnitrone (POBN) and HER generated from either a thermi c decomposition of 1,1'-dihydroxyazoethane (DHAE) or a Fenton reaction syst em containing ethanol was markedly diminished by the addition of mitochondr ia, indicating an interaction between HER and mitochondria. Exposure of rat liver mitochondria to HER generated from either system caused swelling, as reflected by a decrease in absorbance at 540 nm, in a HER concentration-de pendent and a cyclosporin A-sensitive manner. Mitochondrial swelling was al so induced in the Fenton reaction system without ethanol. The DHAE-dependen t generation of HER in mitochondrial suspension resulted in a decrease of m embrane protein thiols and collapse of the membrane potential (Delta Psi). The swelling induced by HER was prevented by glutathione and vitamin E, but not by superoxide dismutase. Catalase did not prevent the swelling caused by the acetaldehyde/hydroxylamine O-sulfonate (HOS) system, but was inhibit ory in the Fenton reaction system with or without ethanol. These results in dicate that HER, as well as hydroxyl radical, can induce the MPT, and sugge st the possibility that the collapse of Delta Psi caused by HER may, at lea st in part, contribute to impairment of mitochondrial function caused by et hanol and in ethanol-induced Liver injury. (C) 2000 Elsevier Science Inc.