Effects of pycnogenol on the microsomal metabolism of the tobacco-specific nitrosamine NNK as a function of age.
NNK is a potent environmental carcinogen to which smokers and non-smokers are 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-hydroxylation was the major pathway in lung microsomes irrespective of age. Pycnogenol (40 and 120 microg/ml) exhibited a statistically significant inhibition of carbonyl reduction and alpha-hydroxylation pathways in liver microsomes from both age groups and in addition to these pathways, pycnogenol inhibited the N-oxidation pathway in lung microsomes. The liver and lung microsomes from 20-month-old rats were less active than from 6-month-old rats although the difference was not statistically significant.
Huynh
H T
HT
Department of Physiology and Pharmacology, Loma Linda University, School of Medicine, CA 92350, USA.
Teel
R W
RW
D000375:Aging / Q000502:physiology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006900:Hydroxylation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000187:drug effects* / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009602:Nitrosamines / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010936:Plant Extracts; D010947:Plants, Toxic; D051381:Rats; D011916:Rats, Inbred F344; D014026:Nicotiana / Q000737:chemistry
D005419:Flavonoids; D016166:Free Radical Scavengers; D009602:Nitrosamines; D010936:Plant Extracts; C024070:pycnogenols; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone