Effects of pycnogenol on the microsomal metabolism of the tobacco-specificnitrosamine NNK as a function of age

NNK is a potent environmental carcinogen to which smokers and non-smokers a re exposed. The response to NNK can be altered by various factors including nutrition. In this study, we examined the effects of pycnogenol on the in vitro metabolism of the tobacco-specific nitrosamine NNK by liver and lung microsomes from 6- and 20-month-old male F344 rats. The major NNK metabolic pathway in liver microsomes was carbonyl reduction, while alpha-hydroxylat ion was the major pathway in lung microsomes irrespective of age. Pycnogeno l (40 and 120 mu g/ml) exhibited a statistically significant inhibition of carbonyl reduction and alpha-hydroxylation pathways in liver microsomes fro m both age groups and in addition to these pathways, pycnogenol inhibited t he N-oxidation pathway in lung microsomes. The liver and lung microsomes fr om 20-month-old rats were less active than from 6-month-old rats although t he difference was not statistically significant. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.