Relationship between the carbon skeleton length of ketonic solvents and potentiation of chloroform-induced hepatotoxicity in rats.
Previous studies have suggested that ketonic solvents potentiate the hepatotoxic action of CHCl3 in rats. In addition, the relative potentiating capacity of the ketones appeared to be related to the length of their carbon skeleton. To test this hypothesis CHCl3-induced liver injury was evaluated in male Sprague-Dawley rats pretreated (15 mmol/kg, p.o.) with acetone (Ac), 2-butanone (Bu), 2-pentanone (Pn), 2-hexanone (Hx) or 2-heptanone (Hp). After 18 h, a challenging dose of CHCl3, (0.50 or 0.75 ml/kg, i.p.) was given. Liver damage was evaluated 24 h after CHCl3 administration by determining elevations in plasma GPT and OCT activity. Neither Ac, Bu, Pn, Hx, Hp or the CHCl3 challenging dosages produced marked liver injury when given alone. However, each of the ketones potentiated CHCl3-induced liver damage. The severity of the potentiated hepatotoxic response was significantly (positively) correlated with the ketone carbon chain length. These observations suggest that carbon skeleton length may play a role in determining the relative potentiating capacity of ketonic solvents.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D002725:Chloroform / Q000633:toxicity*; D004357:Drug Synergism; D007659:Ketones / Q000633:toxicity*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009954:Ornithine Carbamoyltransferase / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012997:Solvents / Q000633:toxicity*; D013329:Structure-Activity Relationship
D007659:Ketones; D012997:Solvents; D002725:Chloroform; D009954:Ornithine Carbamoyltransferase; D000410:Alanine Transaminase