Hepatotoxicity and lethality of halomethanes in Mongolian gerbils pretreated with chlordecone, phenobarbital or mirex.
The hepatotoxic and lethal effects of CBrCl3, CCl4 and CHCl3 were investigated in gerbils with or without prior exposure to dietary chlordecone (CD), phenobarbital (PB) and mirex (MX) at 10, 225 and 10 ppm, respectively, for 15 days. Gerbils were quite sensitive to these halomethanes (48 h LD50: 20, 80 and 400 microliters/kg, respectively). CD, known to potentiate hepatotoxic and lethal effects of halomethanes in rats, failed to potentiate the toxic effects of any of these three halomethanes in gerbils. PB and MX were also ineffective. Since stimulation of early hepatocellular regeneration has been shown to be responsible for the recovery from the toxicity of a low dose of CCl4, liver cell regeneration and tissue repair were studied in gerbils after CCl4 administration. The objectives of these studies were to investigate the possible reasons for the high sensitivity of gerbils to halomethane toxicity and to investigate the mechanism for their refractoriness to CD-potentiated halomethane toxicity. A low and a high dose of CCl4 (15 and 80 microliters/kg, i.p. respectively) were used to study the time-course of liver injury in gerbils pretreated with or without CD. The low dose of CCl4 stimulated cellular regeneration as indicated by the increase of 3H-thymidine (3H-T) incorporation in hepatic nuclear DNA. The cellular regeneration and tissue repair activities resulted in complete recovery from the limited liver injury in both CD-pretreated and control gerbils. In contrast to rats, however, the process of cell division in gerbils occurred much later, 2 days after CCl4 administration. Evidence from histomorphometric studies was consistent with serum enzyme and 3H-T incorporation data.(ABSTRACT TRUNCATED AT 250 WORDS)
Cai
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
Mehendale
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HM
D000818:Animals; D001975:Bromotrichloromethane / Q000633:toxicity*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D007631:Chlordecone / Q000633:toxicity*; D002725:Chloroform / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005849:Gerbillinae; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008917:Mirex / Q000633:toxicity*; D010634:Phenobarbital / Q000633:toxicity*; D013045:Species Specificity
D002725:Chloroform; D004247:DNA; D002251:Carbon Tetrachloride; D001975:Bromotrichloromethane; D007631:Chlordecone; D010634:Phenobarbital; D008917:Mirex