© 1989 Oxford University Press
research-article |
Comparison of the Hepatotoxicity in Mice and the Mutagenicity of Three Nitroalkanes
Mechanisms of Drug Toxicity Research Group, Pharmaceutical Sciences Institute, Aston University Birmingham B4 7ET
*Department of Pharmacology, University College Dublin, Ireland
Department of Biochemistry, University of Birmingham Birmingham B15 2TJ, United Kingdom
Received November 28, 1988; accepted February 21, 1989
The hepatotoxic and mutagenic potentials of 2-nitropropane, nitromethane, and nitroethane were compared. Hepatotoxicity was assessed biochemically and histopathologically in BALB/c mice. In male mice, plasma activities of the hepatic enzymes sorbitol dehydrogenase, alanine aminotransferase, and aspartate aminotransferase were significantly elevated 48, 72, and 96 hr after ip administration of 9 mmol/kg 2-nitropropane, but not at 24 hr and not after administration of smaller dose of 2-nitropropane nor after nitromethane or nitroethane (9 mmol/lg). In female mice a dose of 6.7 mmol/kg of 2-nitropropane was sufficient to cause hepatotoxicity. The histopathological evaluation supported the biochemical results, and livers of mice that had received 2-nitropropane (9 mmol/kg) showed damage, particularly in the periportal region. Mutagenicity was tested in Salmonella typhimurium tester strains TA98, TA100, and TA102. Both 2-nitropropane and its anionic form, propane-2-nitronate, were mutagenic but the nitronate was the more powerful mutagen. Nitromethane, nitroethane, nor their nitronates caused an increase in the number of revertant colonies over those seen in control plates. The results suggest that the primary nitroalkanes are much less hepatotoxic and mutagenic than 2-nitropropane.