Effects of intragastrically administered Pycnogenol (R) on NNK metabolism in F344 rats

NNK is a tobacco-specific nitrosamine that requires metabolic activation by cytochrome P450 enzymes. NNK may be metabolized via carbonyl reduction, N- oxidation, and a-carbon hydroxylation. Pycnogenol(R) is mixture of flavono id compounds extracted from pine tree bark and is available as a dietary su pplement. We have previously shown that Pycnogenol(R) inhibits the in vitro metabolism of NNK in lung and liver microsomes of F344 rats in a concentra tion-dependent manner. In this report, intragastrically administered Pycnog enol(R) in saline affected NNK metabolism in lung microsomes differently th an in liver microsomes of F344 rats. The administered Pycnogenol(R) was inh ibitory toward NNK activation in lung microsomes but not in liver microsome s suggesting that Pycnogenol(R) may afford chemoprotection toward NNK-induc ed lung tumorigenesis when administered orally but not toward NNK-induced l iver tumorigenesis. The effects of intragastrically administered Pycnogenol (R) on NNK metabolism in lung and liver microsomes were similar in 6 mo and 20 mo old rats although the level of NNK metabolism was less in the 20 mo old animals.