Effect of hyperoxia on liver necrosis induced by hepatotoxins.
We have tested the effects of hyperbaric oxygen on necrosis of rat liver induced by the administration of several toxins. The extent of liver necrosis was determined 24 h after the administration of the toxins by measurement of serum levels of alanine and aspartate amino-transferases and by histologic and ultrastructural analyses. Treatment with hyperbaric oxygen decreases carbon tetrachloride (CCl4)-induced necrosis in a manner dependent upon duration and pressure of oxygen exposure. Pretreatment of rats with phenobarbital diminishes this protective effect. Hyperbaric oxygen treatment before or immediately after CCl4 intoxication is protective. Loss of protection is rapid; hyperbaric oxygen treatment 6 h after CCl4 intoxication augments the liver necrosis. No delayed necrogenic effects of CCl4 are seen in the animals treated with hyperbaric oxygen immediately. Hyperbaric oxygen augments the liver necrosis induced by acetaminophen, bromobenzene, dimethylnitrosamine or thioacetamide. This augmented necrosis is averted by prolonged treatment with hyperbaric oxygen. Hyperbaric oxygen has no effect on liver injury induced by galactosamine or lipopolysaccharide. We conclude that hyperoxia decreases the hepatic necrosis induced by compounds which undergo reductive biotransformation by the cytochrome P-450 monooxygenase system; hyperoxia augments the necrosis induced by compounds which undergo oxidative biotransformation by this system. Biotransformation of toxins appears to be nonspecifically inhibited by hyperoxic exposure of long duration.
D000082:Acetaminophen / Q000506:poisoning; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000150:complications / Q000628:therapy; D056486:Chemical and Drug Induced Liver Injury; D006224:Cricetinae; D006931:Hyperbaric Oxygenation; D008099:Liver / Q000187:drug effects / Q000648:ultrastructure; D008107:Liver Diseases / Q000473:pathology / Q000628:therapy*; D008297:Male; D008647:Mesocricetus; D009336:Necrosis; D010634:Phenobarbital / Q000506:poisoning; D011041:Poisoning / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011919:Rats, Inbred Strains
D000082:Acetaminophen; D010634:Phenobarbital