Protection by chrysin, apigenin, and luteolin against oxidative stress is mediated by the Nrf2-dependent up-regulation of heme oxygenase 1 and glutamate cysteine ligase in rat primary hepatocytes

被引：152

作者：

Huang, Chin-Shiu ^{[2
]}

Lii, Chong-Kuei ^{[1
]}

Lin, Ai-Hsuan ^{[3
]}

Yeh, Yu-Wen ^{[1
]}

Yao, Hsien-Tsung ^{[1
]}

Li, Chien-Chun ^{[3
]}

Wang, Tsu-Shing ^{[4
,5
]}

Chen, Haw-Wen ^{[1
]}

机构：

[1] China Med Univ, Dept Nutr, Taichung, Taiwan

[2] Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung, Taiwan

[3] Chung Shan Med Univ, Dept Nutr, Taichung, Taiwan

[4] Chung Shan Med Univ, Dept Biomed Sci, Taichung, Taiwan

[5] Chung Shan Med Univ Hosp, Dept Med Res, Taichung, Taiwan

来源：

ARCHIVES OF TOXICOLOGY | 2013年 / 87卷 / 01期

关键词：

Extracellular signal-regulated protein kinase 2 (ERK2); Flavones; Heme oxygenase 1 (HO-1); Glutamate cysteine ligase (GCL); Nuclear factor erythroid 2-related factor 2 (Nrf2); GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; PROTEIN-KINASE-C; ADHESION MOLECULE EXPRESSION; ANTIOXIDANT RESPONSE ELEMENT; SUBUNIT GENE; PHOSPHATIDYLINOSITOL; 3-KINASE/AKT; GLUTATHIONE SYNTHESIS; TRANSCRIPTION FACTOR; DIETARY FLAVONOIDS; ENDOTHELIAL-CELLS;

D O I：

10.1007/s00204-012-0913-4

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

Chrysin, apigenin, and luteolin are flavones that differ in their number of hydroxyl groups in the B ring. In this study, we investigated the protection by chrysin, apigenin, and luteolin against tert-butyl hydroperoxide (tBHP)-induced oxidative stress and the possible mechanisms involved in rat primary hepatocytes. Chrysin, apigenin, and luteolin dose-dependently up-regulated the protein expression of heme oxygenase 1 (HO-1) and glutamate cysteine ligase (GCL) catalytic (GCLC) and modifier subunit (GCLM) and increased the intracellular glutathione (GSH) content and the ratio of GSH to oxidized GSH. Among the flavones studied, chrysin showed the greatest induction of HO-1, GCLC, and GCLM protein expression and GSH content. Cellular reactive oxygen species production induced by tBHP was attenuated by pretreatment with chrysin, apigenin, and luteolin (P < .05), and this protection was reversed by the GCL inhibitor l-buthionine-S-sulfoximine and the HO-1 inhibitor zinc protoporphyrin. Chrysin, apigenin, and luteolin activated extracellular signal-regulated protein kinase 2 (ERK2), nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, nuclear Nrf2-antioxidant responsive element (ARE) binding activity, and ARE-dependent luciferase activity. Both ERK2 and Nrf2 siRNAs attenuated chrysin-induced HO-1, GCLC, and GCLM protein expression. Taken together, these results suggest that chrysin, apigenin, and luteolin inhibit tBHP-induced oxidative stress by up-regulating HO-1, GCLC, and GCLM gene transcription via the ERK2/Nrf2/ARE signaling pathways in rat primary hepatocytes.

引用

页码：167 / 178

页数：12

共 56 条

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