Minimal effects of acrylonitrile on pulmonary and hepatic cell injury enzymes in rats with induced cytochrome P450.
Acrylonitrile (AN) has many industrial applications but is a known carcinogen in animals and a suspect human carcinogen. Its toxicity is generally associated with its bioactivation, the initial step of which is epoxidation by cytochrome P450. While the hepatotoxicity and pneumotoxicity of AN in naive rats is generally low, the purpose of this study was to investigate the pneumotoxicity and hepatotoxicity of AN in adult male Sprague-Dawley rats and evaluate interactions with agents that may alter its metabolism. Five agents, phenobarbital, beta-naphthoflavone, pyridine, ethanol, and acetone, were administered prior to AN as inducers of CYP2B, CYP1A, and CYP2E1. Pneumotoxicity was measured as increases in y-glutamyltranspeptidase (GGT) and lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF). Hepatotoxicity was measured as increases in serum sorbitol dehydrogenase (SDH). AN (1 mmol/kg ip) had little effect on liver or lung, even when given following most of the inducing agents. AN (1.5 mmol/kg) caused an increase in GGT, but had little effect on SDH or LDH. Acetone plus AN caused an increase in mortality and some indication of pneumotoxicity, but lung and liver were histologically normal. Thus AN alone even at a high dose had no effect on the liver or lung and minimal effects following induction of cytochrome P450 by acetone.
Felten
R K
RK
School of Health Sciences, Purdue University, West Lafayette, IN 47906, USA.
DeNicola
D B
DB
Carlson
G P
GP
D000096:Acetone; D000181:Acrylonitrile / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D000431:Ethanol; D007527:Isoenzymes / Q000096:biosynthesis*; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010634:Phenobarbital; D011725:Pyridines; D051381:Rats; D017207:Rats, Sprague-Dawley; D019324:beta-Naphthoflavone; D005723:gamma-Glutamyltransferase / Q000032:analysis
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011725:Pyridines; D000096:Acetone; D000431:Ethanol; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D007064:L-Iditol 2-Dehydrogenase; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D000181:Acrylonitrile; C023666:pyridine; D010634:Phenobarbital