AUTOGENOUS PRODUCTION OF HYDROXYL RADICALS FROM THIOPENTAL

It is generally believed that barbiturates can protect neural tissues from the damage induced by cerebral hypoxia. One of the mechanisms for protecting neurons is through the inhibition of lipid peroxidation (L PO). We therefore examined LPO in rat brain, liver and kidney by measu ring the accumulation of thiobarbituric acid-reactive substances (TBAR ) after thiopental administration under 21% O-2. We also designed an i n vitro study to gain insight into free radical generation leading to the formation of LPO from thiopental by electron spin resonance (ESR). An accumulation of TBAR in the rat liver was observed after the admin istration of a large dose of thiopental (70 mg/kg intraperitoneally). However, no change in LPO in the brain and kidney was observed. In the in vitro study, thiopental could scavenge superoxide (O(2)(r)adical a nion) radicals, while it spontaneously generated hydroxyl radicals (. OH) in solution. We conclude that thiopental can scavenge O(2)(r)adica l anion, while producing . OH, subsequently resulting in membrane lipi d peroxidation under physiologic O-2 conditions. This formation of . O H may damage cell membrane lipids.