Effects of intragastrically administered Pycnogenol 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 alpha-carbon hydroxylation. Pycnogenol is a mixture of flavonoid compounds extracted from pine tree bark and is available as a dietary supplement. We have previously shown that Pycnogenol inhibits the in vitro metabolism of NNK in lung and liver microsomes of F344 rats in a concentration-dependent manner. In this report, intragastrically administered Pycnogenol in saline affected NNK metabolism in lung microsomes differently than in liver microsomes of F344 rats. The administered Pycnogenol was inhibitory toward NNK activation in lung microsomes but not in liver microsomes suggesting that Pycnogenol may afford chemoprotection toward NNK-induced lung tumorigenesis when administered orally but not toward NNK-induced liver tumorigenesis. The effects of intragastrically administered Pycnogenol 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.