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. Hepatotoxicity 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 hepatotoxicity. 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.