Potentiation of CCl4 hepatotoxicity and lethality by chlordecone in female rats

Female Sprague-Dawley rats (175-200 g) were maintained on a commercial powdered rat chow containing 0 or 10 ppm chlordecone (Kepone; CD). On day 15 of the dietary protocol, a single dose of CCl4 (5-100 microliters/kg) was administered i.p. in corn oil vehicle. Controls received corn oil vehicle only. Twenty-four hours after CCl4 administration, hepatotoxicity was assessed using biochemical, functional, and histopathological parameters. Serum enzymes (GPT, GOT, ICD and OCT) were elevated in a dose related manner in the animals receiving CD-CCl4 combination. CCl4 alone at the doses used had no marked effect. Centrilobular necrosis was observed in the animals receiving CD-CCl4 combination. Biliary excretion of phenolphthalein glucuronide (PG) and the rate of bile flow were decreased in a dose-dependent manner. Forty-eight hour LD50 of CCl4 was decreased 26-fold by CD pretreatment. These results indicate that CD potentiates CCl4 toxicity in female rats as well. Since the hepatic functional status is greatly compromised, the CD potentiated lethality is preceded by hepatic failure. Furthermore, female rats are sensitized to smaller doses of CCl4 in comparison to male rats.