Potentiation of bromotrichloromethane hepatotoxicity and lethality by chlordecone preexposure in the rat

Abstract

These studies were designed to provide dose-response relationships for chlordecone (CD) potentiation of BrCCl 3 hepatotoxicity in male rats using biochemical, functional and histopathological parameters. The influence of this interaction on BrCCl 3 lethality was also examined. Male Sprague-Dawley rats (175–200g) received a single ip dose of 1, 5, 10, 15 or 25 μL BrCCl 3/kg following a 15 day dietary pretreatment of 0 or 10 ppm CD. Twenty four hrs after BrCCl 3 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 LD 50 of BrCCl 3 was also examined using the method of moving averages. With the exception of 1 μL BrCCl 3/kg dose which had no effect, CD-BrCCl 3 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 BrCCl 3. Extensive centrilobular necrosis was observed in the animals given CD-BrCCl 3 combination and the necrogenic effect was more severe at the doses of 15 μL and 25 μL BrCCl 3/kg. BrCCl 3-lethality was increased 5-fold by CD as indicated by the decreased LD 50. The results suggest that CD-induced BrCCl 3 toxicity is manifested both in the form of hepatotoxicity and lethality and since the hepatic functional status is greatly compromised, the CD potentiatedhepatic failure is related to lethality.