Potentiation of carbon tetrachloride hepatotoxicity by chlordecone: Dose-response relationships and increased covalent binding in vivo
✍ Scribed by Britton, Robert S. ;Dolak, James A. ;Glende, Eric A. ;Recknagel, Richard O.
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- English
- Weight
- 710 KB
- Volume
- 2
- Category
- Article
- ISSN
- 0887-2082
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✦ Synopsis
Chlordecone greatly potentiates carbon tetrachloride (CC14) hepatotoxicity. In order to quantitate the degree of this potentiation, the effects of a range of doses of C C 4 on two microsomal enzymatic functions and liver enzyme release were examined in chlordecone-treated and control rats. Male Sprague-Dawley rats were pretreated with 15 mg chlordecone per kilogram body weight (BW) intragastrically or with vehicle. After 48 hours, 0 to 250 p1 CC14 per 100 g body weight were given intraperitoneally (IP), and the rats were killed 24 hours later. Chlordecone treatment produced approximately a 17-fold potentiation of the CCLdependent loss of cytochrome P-450 and glucose-6-phosphatase activity, so that a dose of 6 pl CC14 per 100 g body weight in the chlordecone-treated animals resulted in a similar amount of damage as observed with 100 p i CC14 per 100 g body weight in controls. A similar potentiation by chlordecone was seen with CC14induced increases in serum glutamic-oxaloacetic transaminase (SGOT) levels. Chlordecone treatment also increased hepatic cytochrome P-450 levels by 67% and resulted in an increase in the covalent binding of [14-C]-CC14-derived metabolites to microsomal protein and lipid in vivo.