Acetone compared to other ketones in modifying the hepatotoxicity of inhaled 1,2-dichlorobenzene in rats and mice

Abstract

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.