Comparison of the effects of pyridine and its metabolites on rat liver and kidney.
In order to evaluate the possibility that the metabolism of pyridine may be important for its toxic actions, pyridine was compared with pyridine N-oxide, 2-hydroxypyridine, 3-hydroxypyridine, 4-hydroxypyridine and pyridinium methyliodide in rats given equal molar doses of the chemicals i.p. Hepatoxicity was assessed by measuring serum sorbitol dehydrogenase, nephrotoxicity by determining increases in blood urea nitrogen and serum creatinine, and influence on xenobiotic metabolism by measuring changes in p-nitrophenol hydroxylase and ethoxyresorufin and benzyloxyresorufin dealkylase activities. After a single dose of 2.5 mmol/kg, pyridinium methyliodide was the only compound that was lethal whereas 2-hydroxypyridine was the only one that caused significant hepatoxicity. Pyridine, pyridine N-oxide, 3-hydroxypyridine and 4-hydroxypyridine were effective inducers of xenobiotic metabolism. Thus the metabolites of pyridine may play a role, either singly or collectively, in the actions of pyridine.
Carlson
G P
GP
School of Health Sciences, Purdue University, West Lafayette, IN 47907-1338, USA.
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000633:toxicity; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism; D011041:Poisoning / Q000401:mortality; D011725:Pyridines / Q000378:metabolism / Q000633:toxicity*; D011726:Pyridinium Compounds / Q000378:metabolism / Q000633:toxicity; D011728:Pyridones / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D000975:Antioxidants; D011725:Pyridines; D011726:Pyridinium Compounds; D011728:Pyridones; C534143:4-pyridone; C023500:3-hydroxypyridine; C017679:2-hydroxypyridine; D003577:Cytochrome P-450 Enzyme System; C013229:pyridine N-oxide; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; C023666:pyridine