MISC

2002年9月

Role of Zn2+ in oxidative stress caused by endoxtoxin challenge

EUROPEAN JOURNAL OF PHARMACOLOGY
  • S Sakaguchi
  • ,
  • Y Iizuka
  • ,
  • S Furusawa
  • ,
  • M Ishikawa
  • ,
  • S Satoh
  • ,
  • M Takayanagi

451
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
DOI
https://doi.org/10.1016/S0014-2999(02)02223-9
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000178327900011&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/S0014-2999(02)02223-9
  • ISSN : 0014-2999
  • Web of Science ID : WOS:000178327900011

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