A superoxide dismutase mimetic with catalase activity (EUK-8) reduces the organ injury in endotoxic shock

McDonald, M.C., Bianca, R.D.D., Wayman, N.S., Pinto, A., Sharpe, M.A., Cuzzocrea, S., Chatterjee, P.K. and Thiemermann, C. (2003) A superoxide dismutase mimetic with catalase activity (EUK-8) reduces the organ injury in endotoxic shock European Journal of Pharmacology, 466 (1-2). pp. 181-189.

Full text not available from this repository.

Abstract

Reactive oxygen species contribute to the multiple organ failure in endotoxic shock. Here, we investigate the effects of a salen-manganese complex, which exhibits both superoxide dismutase and catalase activity (EUK-8), on the circulatory failure, renal and liver injury and dysfunction caused by endotoxin in the anaesthetised rat. Endotoxaemia (6 mg/kg i.v., Escherichia coli lipopolysaccharide) for 6 h caused hypotension, renal dysfunction and liver injury. Treatment of rats with EUK-8 (0.3 or 1 mg/kg bolus injection followed by an infusion of 0.3 or 1 mg/kg/h) attenuated the renal and liver injury and dysfunction in a dose-related fashion. In addition, the higher dose of EUK-8 attenuated the delayed hypotension caused by endotoxin in the rat. Thus, an enhanced formation of reactive oxygen species importantly contributes to the circulatory failure, as well as the organ injury and dysfunction associated with endotoxic shock. We propose that small molecules, which have the catalytic activity of both superoxide dismutase and catalase, may represent a novel therapeutic approach for the therapy of endotoxic shock.

Item Type: Journal article
Uncontrolled Keywords: Oxygen radical; Superoxide dismutase; EUK-8; EUK-134; Superoxide anion; Multiple organ failure; Shock
Subjects: B000 Health Professions > B100 Anatomy Physiology and Pathology
DOI (a stable link to the resource): 10.1016/S0014-2999(03)01538-3
Faculties: Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences
Depositing User: editor spbs
Date Deposited: 06 Nov 2007
Last Modified: 05 Jun 2013 10:41
URI: http://eprints.brighton.ac.uk/id/eprint/434

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year