PMID: 8937894Nov 1, 1996Paper

Vitamin A potentiation of vinylidene chloride hepatotoxicity in rats and precision-cut rat liver slices

Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology
J B WueweeraK Brendel

Abstract

Pretreatment of large doses of vitamin A (VA) is known to potentiate the hepatotoxicity of carbon tetrachloride. Therefore the effects of 1-day VA pretreatment on VDC hepatotoxicity was examined both in vivo and in an in vitro system of precision-cut rat liver slices. Male Sprague-Dawley rats were pretreated with 250,000 IU/kg VA by oral gavage. After 24 hr rats were administered 50, 100, or 200 mg/kg VDC ip. Precision-cut liver slices were prepared from VA pretreated rats 24 hr later and the liver slices were exposed for 2-8 hr to 0.025-1.0 microliter VDC evaporated into the gas phase of the incubation vials. VA pretreatment resulted in an enhancement of VDC toxicity, both in vivo and in vitro. There was a dose-dependent increase in plasma ALT 24 hr after VDC treatment of rats and an increase in K+ leakage from liver slices after VDC exposure. Histological analysis of the liver or the liver slices revealed that VA + VDC treatment resulted in centrilobular necrosis of the liver. When GdCl3 (10 mg/kg iv) was administered just before VA pretreatment of rats, VDC toxicity was partially reversed as observed by a decrease in ALT in vivo and a decrease in the loss of K+ in vitro. These results indicated that Kupffer cells, the reside...Continue Reading

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