Acetone compared to other ketones in modifying the hepatotoxicity of inhaled 1,2-dichlorobenzene in rats and mice.
The ability of acetone and 3 other ketone vapours to influence the hepatotoxicity of inhaled 1,2-dichlorobenzene (DCB) was examined in rats and mice. Methylethylketone, methylisobutylketone or cyclohexanone increased liver cytochrome P-450 content and glutathione-S-transferase (GST) activity, but did not affect serum glutamate dehydrogenase (GLDH) activity in rats. Pre-exposure to these ketones enhanced DCB-induced increase in serum GLDH activity (8-63-fold), while the increases in cytochrome P-450 content (33-86%) and GST activity (42-64%) were identical to those resulting from exposure to ketones alone. Each of the 3 levels of exposure to acetone elicited cytochrome P-450 and GST responses comparable with those caused by the other ketones. In spite of that, acetone pre-exposure potentiated (4785 ppm), reduced (10670 ppm) or suppressed (14790 ppm) DCB-induced liver toxicity. In mice, the 3 ketones mentioned above interacted with DCB on centrolobular liver glucose-6-phosphatase (G-6-Pase) while acetone pre-exposure elicited an interactive G-6-Pase response in the mediolobular area alone, suggesting topographic change.
Brondeau
M T
MT
Institut National de Recherche et de Sécurité Vandoeuvre, France.
Ban
M
M
Bonnet
P
P
Guenier
J P
JP
de Ceaurriz
J
J
D000096:Acetone / Q000494:pharmacology*; D000280:Administration, Inhalation; D000818:Animals; D002074:Butanones / Q000494:pharmacology; D002722:Chlorobenzenes / Q000008:administration & dosage / Q000633:toxicity*; D003512:Cyclohexanones / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000097:blood; D004347:Drug Interactions; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D005969:Glutamate Dehydrogenase / Q000096:biosynthesis / Q000097:blood; D005982:Glutathione Transferase / Q000378:metabolism; D007659:Ketones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008742:Methyl n-Butyl Ketone / Q000494:pharmacology; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains
D002074:Butanones; D002722:Chlorobenzenes; D003512:Cyclohexanones; D007659:Ketones; D000096:Acetone; C004726:2-dichlorobenzene; D008742:Methyl n-Butyl Ketone; D003577:Cytochrome P-450 Enzyme System; D005969:Glutamate Dehydrogenase; D005982:Glutathione Transferase; D005952:Glucose-6-Phosphatase; C005458:methyl isobutyl ketone