Effect of antioxidants, resveratrol, quercetin,... : Hepatology (original) (raw)
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Effect of antioxidants, resveratrol, quercetin, and N -acetylcysteine, on the functions of cultured rat hepatic stellate cells and kupffer cells
Kawada, Norifumi M.D.*, 1; Seki, Shuichi1; Inoue, Masayasu2; Kuroki, Tetsuo1
1Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan
2Department of Biochemistry, Osaka City University Medical School, Osaka, Japan
*Address reprint requests to: Third Department of Internal Medicine, Osaka City University Medical School, 1-5-7, Asahimachi, Abeno, Osaka 545, Japan. Fax: 81-6-645-2416.
Received October 14, 1997; Accepted January 09, 1998; previously published online December 30, 2003
Abstract
Effects of antioxidants, resveratrol, quercetin, and _N_-acetylcysteine (NAC) on the functions of cultured rat hepatic stellate cells and Kupffer cells were studied. These compounds dose-dependently suppressed serum-dependent proliferation of stellate cells as determined by [3H]thymidine and 5-bromo-2′-deoxyuridine uptake. Expression of smooth muscle α-actin was suppressed by a high dose of resveratrol and quercetin. These phenolic compounds also suppressed inositol phosphate metabolism, tyrosine phosphorylation, and mitogen-activated protein (MAP) kinase activation in platelet-derived growth factor/BB-stimulated stellate cells. Moreover, the phenolic compounds selectively reduced the level of cell cycle protein cyclin D1 in stellate cells. Thus, resveratrol and quercetin might inhibit stellate cell activation by perturbing signal transduction pathway and cell cycle protein expression, whereas mechanism of potent antiproliferative effect of NAC remains to be elucidated. On the other hand, kinetic analysis showed that production of nitric oxide (NO) and tumor necrosis factor α (TNF-α) by lipopolysaccharide-stimulated Kupffer cells was strongly inhibited by resveratrol and quercetin but not by NAC. Although expression of messenger RNAs for inducible NO synthase and TNF-α was not affected by the phenolic compounds, cellular levels of inducible NO synthase and TNF-α secretion were suppressed significantly, indicating the posttranscriptional process of generating these proteins might be affected predominantly by these phenolic compounds. Thus, NAC and these phenolic compounds may have therapeutic potential against liver injury by regulating functions of hepatic stellate cells and Kupffer cells.
Copyright © 1998 American Association for the Study of Liver Diseases.