Green tea polyphenols and tannic acid act as potent inhibitors of phorbol ester-induced nitric oxide generation in rat hepatocytes independent of their antioxidant properties

The deleterious effects of excessive release of nitric oxide (NO) have been implicated in the tissue damage and inflammation. In this study, the effec t of various flavonoids and other oxidant scavenging chemical agents have b een studied for their ability to inhibit 12-O-tetradecanoyl phorbol 13-acet ate (TPA)-induced NO generation in rat hepatocyte. Hepatocytes activated wi th TPA (25-200 nM) released NO in a concentration- and time-dependent manne r. Green tea polyphenols (GTP) and tannic acid (TA) were most effective in inhibiting TPA-induced NO generation (90%). These agents were also effectiv e in inhibiting NO formation when added 2 h following TPA addition. The oth er oxidant scavengers, such as L-histidine, sodium azide, vitamin E and sod ium benzoate, were not found to be effective even up to 1.0 mM concentratio n. These results suggest that TA and GTP are potent inhibitors of NOS activ ity and the inhibition of TPA-induced NO generation by these polyphenols is independent of their antioxidant activity. It is tempting to speculate tha t these agents could be utilized in the pharmacological manipulations of NO -dependent pathophysiological responses. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.