Hyperbaric oxygen protection against carbon tetrachloride hepatotoxicity in the rat. Association with altered metabolism.
Because reports have appeared suggesting that hyperbaric O2 treatment protects against the hepatotoxicity of CCl4 in humans, studies were undertaken in rats to assess this possibility and to explore its mechanism. Treatment with 2 atm of O2 for 6 h after intragastric administration of CCl4 (2.6 mmol/100 g) improved survival from 31% to 96%. The same treatment administered 24 h after the CCl4 improved survival from 36% to 50%. The protective effect does not appear to be mediated through changes in excretion or distribution because exhalation of CCl4 was not increased, and hepatic CCl4 concentration was not decreased by hyperbaric O2. Changes in CCl4 metabolism were observed, which could explain the protection. Hyperbaric O2 treatment inhibited in vivo conversion of CCl4 to its volatile metabolites CHCl3 and CO2 by 52% in the 10 h following CCl4 dosing. The predominant effect was on CO2, which is quantitatively the more significant metabolite. Studies with hepatic microsomes isolated from these rats demonstrated that hyperbaric O2 treatment diminished their capacity to metabolize CCl4 to CO2, and O2-dependent process. It had no effect on the metabolism of CCl4 to CHCl3, an O2-inhibited process. These results indicate that hyperbaric O2 suppresses the microsomal mechanism for metabolizing CCl4 in the presence of O2. Because the mechanism of CCl4 hepatotoxicity is thought to be the same in the rat and in humans, hyperbaric O2 therapy is recommended for treatment of CCl4 poisoning in humans.
D000818:Animals; D002251:Carbon Tetrachloride / Q000009:adverse effects* / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D006931:Hyperbaric Oxygenation; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D011041:Poisoning / Q000628:therapy*; D051381:Rats; D011919:Rats, Inbred Strains
D002251:Carbon Tetrachloride