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 m ay be important for its toxic actions, pyridine was compared with pyri dine N-oxide, 2-hydroxypyridine, 3-hydroxypyridine, 4-hydroxypyridine and pyridinium methyliodide in rats given equal molar doses of the che micals i.p. Hepatotoxicity was assessed by measuring serum sorbitol de hydrogenase, nephrotoxicity by determining increases in blood urea nit rogen 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 he patotoxicity. Pyridine, pyridine N-oxide, 3-hydroxypyridine and 4-hydr oxypyridine were effective inducers of xenobiotic metabolism. Thus the metabolites of pyridine may play a role, either singly or collectivel y, in the actions of pyridine.