Potentiation of bromotrichloromethane hepatotoxicity and lethality by chlordecone preexposure in the rat.
These studies were designed to provide dose-response relationships for chlordecone (CD) potentiation of BrCCl3 hepatotoxicity in male rats using biochemical, functional and histopathological parameters. The influence of this interaction on BrCCl3 lethality was also examined. Male Sprague-Dawley rats (175-200 g) received a single ip dose of 1, 5, 10, 15 or 25 microL BrCCl3/kg following a 15 day dietary pretreatment of 0 or 10 ppm CD. Twenty four hrs after BrCCl3 challenge, biliary excretion of phenolphthalein glucuronide (PG), bile flow, serum transaminases (SGOT and SGPT), serum ICD and OCT were examined as functional and biochemical indices of hepatic injury. Effect of CD on 48 hr LD50 of BrCCl3 was also examined using the method of moving averages. With the exception of 1 microL BrCCl3/kg dose which had no effect, CD-BrCCl3 combination resulted in potentiation of hepatotoxicity by all parameters examined. Activity of all the serum enzymes was elevated in a dose related manner. A dose related decrease in the biliary excretion of PG and bile flow was observed. These effects were more pronounced at the higher doses of BrCCl3. Extensive centrilobular necrosis was observed in the animals given CD-BrCCl3 combination and the necrogenic effect was more severe at the doses of 15 microL and 25 microL BrCCl3/kg. BrCCl3-lethality was increased 5-fold by CD as indicated by the decreased LD50. The results suggest that CD-induced BrCCl3 toxicity is manifested both in the form of hepatotoxicity and lethality and since the hepatic functional status is greatly compromised, the CD potentiated hepatic failure is related to lethality.
D000818:Animals; D001646:Bile / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D001975:Bromotrichloromethane / Q000378:metabolism / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D007631:Chlordecone / Q000633:toxicity*; D002725:Chloroform / Q000031:analogs & derivatives*; D004357:Drug Synergism; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D007306:Insecticides; D002725:Chloroform; D001975:Bromotrichloromethane; D001663:Bilirubin; D007631:Chlordecone