2002年9月
Role of Zn2+ in oxidative stress caused by endoxtoxin challenge
EUROPEAN JOURNAL OF PHARMACOLOGY
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- 巻
- 451
- 号
- 3
- 開始ページ
- 309
- 終了ページ
- 316
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1016/S0014-2999(02)02223-9
- 出版者・発行元
- ELSEVIER SCIENCE BV
The role of Zn2+ in oxidative stress during endotoxemia was investigated. In rats fed a Zn2+ -deficient diet (Zn2+ concentration of less than 1.5 mg/kg) for 8 weeks, the Zn2+ level in the serum was about 62% lower than that in rats fed a Zn2+-adequate diet (Zn2+ concentration, 50 mg/kg). The Zn2+ level in serum 18 h after administration of endotoxin (6 mg/kg, i.p.) to Zn2+ -deficient diet rats was markedly lower than that of the endotoxin/Zn2+ -adequate diet group. Lipid peroxide formation in the liver of Zn2+ -deficient diet rats was markedly increased 18 h after endotoxin injection compared with that in the endotoxin/Zn2+ -adequate diet group. Metallothionein in the liver of endotoxin/Zn2+ -adequate diet rats was increased more than 17-fold by endotoxin administration, while a markedly lower level of metallothionein was observed in the endotoxin/Zn2+ -deficient diet group. On the other hand, treatment with ZnSO4 (100 muM) significantly increased endotoxin (1 mug/ml)-induced tumor necrosis factor-alpha. (TNF-alpha) production in J774A.1 cells. Our results clearly demonstrated that treatment with ZnSO4 significantly inhibited the endotoxin-induced increase in intracellular Ca2+ level in J774A.1 cells. However, a cell membrane-permeable Zn2+ chelator, N,N,N,N-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN, 1 muM), did not affect the endotoxin-induced TNF-alpha production or Ca2+ level in J774A.1 cells. In addition, we investigated whether Zn2+ can suppress nitric oxide (NO) generation and cytotoxicity in endotoxin-treated cells. Treatment with ZnSO4 (50 muM) significantly inhibited endotoxin-induced NO production in J774A.1 cells, but did not affect endotoxin-induced cytotoxicity. These findings suggest that zinc may play an important role, at least in part, in the oxidative stress during endotoxemia. (C) 2002 Published by Elsevier Science B.V.
- リンク情報
- ID情報
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- DOI : 10.1016/S0014-2999(02)02223-9
- ISSN : 0014-2999
- Web of Science ID : WOS:000178327900011