Potentiation of carbon tetrachloride induced hepatotoxicity by thinner inhalation.
The interaction of thinner and carbon tetrachloride (CCl4) induced hepatotoxicity was studied in the rats using the activity of plasma GOT and GPT, liver triglyceride and histopathologic changes of liver necrosis as indices. The animals were housed in a chamber with the continuous flow of thinner vapour (1.11 g/litre/hr) for 2 hrs prior to i.p. administration of CCl4 (0.1 ml/kg BW) at 18 hrs after thinner inhalation. Thinner inhalation potentiated CCl4 induced hepatotoxicity in a dose-dependent manner. The maximal enhanced effect was observed at 24 hrs after CCl4 administration by which the activities of PGOT and PGPT were significantly increased (3 folds). Thinner itself caused an additive effect on CCl4 induced liver triglyceride accumulation. At 18 hrs after thinner inhalation, the activity of NADPH cytochrome C reductase was markedly increased (2.2 folds) but no change in the activity of aminopyrine N-demethylase which was able to increase the 14.CCl3 free radicals and binding to both the hepatic microsomal proteins (1.8 folds) and lipids (1.4 folds). In addition, thinner pretreatment somehow increased hepatic lipid peroxidation by 1.4 folds. These results suggest that thinner pretreatment causes an increase in mixed function oxidases to activate the formation of .CCl3 free radicals and binding to the microsomal proteins and lipids, which in turn stimulate hepatic damage via lipid peroxidation in the membrane.
Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
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Toskulkao
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Nhongsaeng
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Glinsukon
D000280:Administration, Inhalation; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000378:metabolism / Q000633:toxicity*; D004357:Drug Synergism; D008054:Lipid Peroxides / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D006899:Mixed Function Oxygenases / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D012997:Solvents / Q000633:toxicity*
D008054:Lipid Peroxides; D012997:Solvents; D002251:Carbon Tetrachloride; D006899:Mixed Function Oxygenases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase