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THE GENERATION OF HYDROXYL RADICALS IN BIOLOGIC SYSTEMS: TOXICOLOGICAL ASPECTS
Author(s) -
Cohen Gerald
Publication year - 1978
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1978.tb06993.x
Subject(s) - chemistry , radical , hydroxyl radical , autoxidation , thiourea , superoxide dismutase , hydrogen peroxide , catalase , superoxide , photochemistry , organic chemistry , antioxidant , enzyme
— The formation of hydroxyl radicals in vitro was studied through their reaction with 2‐keto‐4‐thiomethylbutyric acid to form ethylene gas. The autoxidation reaction of 6‐aminodopamine served as a model source of hydroxyl radicals. Ethylene production was suppressed by catalase and by superoxide dismutase, indicating that both hydrogen peroxide and superoxide were involved in the reaction. Hydroxyl radical scavengers (thiourea > benzoate > ethanol) suppressed ethylene production in good agreement with their respective rate constants for reaction with hydroxyl radicals. Urea served as a negative control. Several substituted thiourea derivatives also suppressed ethylene production to a similar degree as thiourea itself. Biologic studies centered on several cytotoxic agents whose mechanisms of action are thought to involve hydroxyl radicals. These agents included alloxan, which destroys the beta cells of the pancreas, and 6‐hydroxy‐ and 6‐aminodopamine, which destroy sympathetic nerves. Damage to tissues in vivo was blocked to varying degrees by pretreatment of animals with hydroxyl radical scavengers such as ethanol or the thiourea derivatives. In addition, hydroxyl radical scavengers blocked the action of 5,7‐dihydroxytryptamine, a neurotoxin whose effects on noradrenaline neurons were previously shown to be blocked by inhibitors of monoamine oxidase. The data indicate that these cell toxins produce their damaging actions on specific target cells through the intracellular generation of hydroxyl radicals.