Studies on the interaction of barbiturates with reactive oxygen radicals: implications regarding barbiturate protection against cerebral ischaemia.
Although the molecular basis of ischaemic damage of the brain is as yet unknown, it has been postulated that the uncontrolled production of reactive oxygenated species derived from molecular oxygen (including hydroxyl radicals, superoxide radicals and singlet oxygen) may play a major role in the production of such injury. The ability of various barbiturates to modify the nature and extent of membrane damage produced by various oxygen radicals generated under well-defined conditions in vitro has been directly examined using the human erythrocyte as model membrane system. Our results indicate that barbiturates are unlikely to exert their protective effects by directly scavenging singlet oxygen, superoxide or hydroxyl radicals. The highly lipophilic barbiturate thiopentone is capable of decreasing the susceptibility of membranes to oxidative degradation by a direct membrane action, a property shared by amphipathic membrane stabilizers such as propranolol. The barbiturates were found to stabilize the haeme moiety of haemoglobin preventing its conversion to methaemoglobin in the presence of hydrogen peroxide. It is postulated that a major aspect of barbiturate action in decreasing ischaemic injury to the brain may involve the stabilization of haeme-coordinated iron complexes, thereby preventing the participation of these ubiquitous substances in initiating and potentiating free radical-mediated processes which have been implicated in the production of such injury.
D001463:Barbiturates / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000517:prevention & control*; D055598:Chemical Phenomena; D002621:Chemistry; D004912:Erythrocytes / Q000187:drug effects; D005609:Free Radicals; D006801:Humans; D008567:Membranes, Artificial; D008708:Methemoglobinemia / Q000139:chemically induced; D009566:Nitrates / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D010545:Peroxides / Q000378:metabolism; D010782:Photolysis; D014969:Xanthine Oxidase / Q000378:metabolism
D001463:Barbiturates; D005609:Free Radicals; D008567:Membranes, Artificial; D009566:Nitrates; D010545:Peroxides; C031618:sodium nitrate; D014969:Xanthine Oxidase