1,3-Butanediol-induced increases in ketone bodies and potentiation of CCl4 hepatotoxicity.
Evidence previously reported suggest that 1,3-butanediol (BD) enhances the hepatotoxic effect of a single small dose of carbon tetrachloride (CCl4) in a dose-related manner. The present study provides additional information concerning the quantitative relationship between the severity of the ketotic state produced by BD and the magnitude of the potentiation observed and emphasizes the use of ketone bodies (KB) to predict the potential hazard of the BD-CCl4 interaction. Liver damage was modulated in male Sprague-Dawley rats by varying the concentration of the BD solutions ingested prior to a CCl4 challenge (0.1 ml/kg, i.p.). These data were compared to ketone bodies in plasma, hepatic tissue and urine. BD produced a dose-dependent metabolic ketosis observable at dosages between 1.1 and 9.9 g/kg per day given for 7 days. Plasma and liver data correlated well together. Concomitantly, potentiation of the CCl4-induced liver injury was also dose-related for the same dosage range; the minimum effective dosage of BD for potentiation was estimated as 1.1 g/kg per day. The linear correlations between hepatic or plasma KB values and the indices of hepatic dysfunction (ALT, OCT) were highly significant. Using a semiquantitative method, a correlation was also found for the urinary KB data. These results suggest that plasma KB concentrations might be useful for predicting possible potentiation of the hepatonecrotic effect of CCl4 by BD.
D000138:Acidosis / Q000139:chemically induced*; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002072:Butylene Glycols / Q000633:toxicity*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004357:Drug Synergism; D007657:Ketone Bodies / Q000097:blood / Q000378:metabolism*; D007662:Ketosis / Q000139:chemically induced*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D002072:Butylene Glycols; D007657:Ketone Bodies; C028491:1,3-butylene glycol; D002251:Carbon Tetrachloride