Potentiation of CCl 4 hepatotoxicity and lethality by chlordecone in female rats

Abstract

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 CCl 4 (5 -100 μl/kg) was administered i.p. in corn oil vehicle. Controls received oil vehicle only. Twenty-four hours after CCl 4 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-CCl 4 combination. CCl 4 alone at the doses used had no marked effect. Centrilobular necrosis was observed in the animals receiving CD-CCl 4 combination. Biliary excretion of phenolphthalein glucuronide (PG) and the rate of bile flow were decreased in a dose-dependent manner. Forty-eight hour LD 50 of CCl 4 was decreased 26-fold by CD pretreatment. These results indicate that CD potentiates CCl 4 toxicity in female rats as well. Since the hepatic functional status is greatly compromized, the CD potentiated lethality is preceded by hepatic failure. Furthermore, female rats are sensitized to smaller doses of CCl 4 in comparison to male rats.