The Effect of Dietary Exposure to a Mirex Plus Chlordecone Combination on CCl4 Hepatotoxicity

The Effect of Dietary Exposure to a Mirex Plus Chlordecone Combinationon CCl₄ Hepatotoxicity. BELL, A. N., AND MEHENDALE, H. M. (1985).Fundam. Appl. Toxicol. 5, 679–687. The purpose of thesestudies was to investigate the effect of a mirex plus chlordeconecombination on CCl₄-induced hepatotoxicity. Male Sprague-Dawleyrats were maintained on control diet or on diets containing10 ppm chlordecone (CD), 10 ppm mirex (M), or M plus CD (10ppm each; MCD) for 15 days. On Day 15 the rats received a singleip injection of CCl₄ (100 µl/kg) and hepatotoxicity wasassessed 24 hr later. Animals in the control group receivingCCU alone were unaffected. Significant increases in liver-to-bodyweight ratios were observed in all three pretreatment groupsfollowing CCl₄ challenge. Increases in serum enzymes (SGPT,SGOT, and ICD) occurred in all three pretreatment groups withCD = MCD > M > control. While MCD and CD pretreatmentled to significant cholestasis and decreases in PG excretion,no such effect was observed with M. Light microscopic examinationof tissues revealed swollen hepatocytes (balloon cells), hepatocellularnecrosis, and lipid accumulation in the MCD, CD, and M groupsfollowing CCl₄ challenge. In summary, as assessed by serum enzymeelevation, biliary flow and hepatic excretory function, M pretreatmentled to only a slight increase in CCl₄ hepatotoxicity. The MCDcombination pretreatment did not potentiate hepatotoxicity abovethat seen with CD alone. These results provide additional evidencethat CD pretreatment results in a rather specific sensitizationof animals to CCl₄ toxicity in ways independent Of the actionsOf M