The effect of dietary exposure to a mirex plus chlordecone combination on CCl4 hepatotoxicity

The purpose of these studies was to investigate the effect of a mirex plus chlordecone combination on CCl4-induced hepatotoxicity. Male Sprague-Dawley rats were maintained on control diet or on diets containing 10 ppm chlordecone (CD), 10 ppm mirex (M), or M plus CD (10 ppm each; MCD) for 15 days. On Day 15 the rats received a single ip injection of CCl4 (100 microliters/kg) and hepatotoxicity was assessed 24 hr later. Animals in the control group receiving CCl4 alone were unaffected. Significant increases in liver-to-body weight ratios were observed in all three pretreatment groups following CCl4 challenge. Increases in serum enzymes (SGPT, SGOT, and ICD) occurred in all three pretreatment groups with CD = MCD greater than M greater than control. While MCD and CD pretreatment led to significant cholestasis and decreases in PG excretion, no such effect was observed with M. Light microscopic examination of tissues revealed swollen hepatocytes (balloon cells), hepatocellular necrosis, and lipid accumulation in the MCD, CD, and M groups following CCl4 challenge. In summary, as assessed by serum enzyme elevation, biliary flow and hepatic excretory function, M pretreatment led to only a slight increase in CCl4 hepatotoxicity. The MCD combination pretreatment did not potentiate hepatotoxicity above that seen with CD alone. These results provide additional evidence that CD pretreatment results in a rather specific sensitization of animals to CCl4 toxicity in ways independent of the actions of M.