Effect of pretreatment with cimetidine or phenobarbital on lipoperoxidation in carbon tetrachloride- and trichloroethylene-dosed rats.
Lipid peroxidation (LP) in vivo as reflected by the exhalation of ethane and n-pentane and by thiobarbituric acid reactive substances (TBARS) in liver microsomes was studied in rats injected with carbon tetrachloride (CCl4) and trichloroethylene (TCE), each at 2 dose levels. Interactions between these chlorinated solvents and cimetidine (CM), an inhibitor of cytochrome P-450-dependent monooxygenases, or phenobarbital (PB) the well known inducer of microsomal enzyme activities were also assessed. A non-hepatotoxic dose of CCl4 did not cause a significant increase in ethane production except in PB-induced rats but did enhance n-pentane elimination, whereas an hepatotoxic dose increased the emission of both hydrocarbons. No interaction between CM and CCl4 could be shown but, as expected, PB potentiated the effect of CCl4. TCE administration led to a moderate dose-independent elevation of n-pentane production but did not affect that of ethane and the effect of TCE was smaller in PB-induced than in CM- or non-pretreated rats. There was no difference in microsomal TBARS content in rats injected with the chlorinated hydrocarbons. The use of butylated hydroxytoluene (BHT) and ethylene diaminetetraacetic acid (EDTA) revealed that direct measurement of TBARS gave inadequate results due to substantial chemical LP in vitro during the whole procedure. With the "ethane-pentane test" it was established that: CM cannot prevent CCl4-induced LP; and TCE hepatotoxicity does not involve increased LP of membrane lipids.
D000473:Alkanes / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002927:Cimetidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013858:Thiobarbiturates / Q000378:metabolism; D014241:Trichloroethylene / Q000633:toxicity*
D000473:Alkanes; D008054:Lipid Peroxides; D013858:Thiobarbiturates; D014241:Trichloroethylene; D002927:Cimetidine; D002251:Carbon Tetrachloride; C029684:thiobarbituric acid; D010634:Phenobarbital