Comparison of the effects of the superoxide dismutase mimetics EUK-134 and tempol on paraquat-induced nephrotoxicity

Samai, M., Sharpe, M.A., Gard, P.R. and Chatterjee, P.K. (2007) Comparison of the effects of the superoxide dismutase mimetics EUK-134 and tempol on paraquat-induced nephrotoxicity Free Radical Biology and Medicine, 43 (4). pp. 528-534. ISSN 0891-5849

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Abstract

Paraquat-induced nephrotoxicity involves severe renal cell damage caused by reactive oxygen species (ROS), specifically via increasing concentrations of superoxide anions in the kidney. Recently, superoxide dismutase (SOD) mimetics (SODm) have been developed that display safe SOD activities but which also possess additional antioxidant enzyme (e.g., catalase) or ROS-scavenging activities. The aim of this study was to compare the effects of two such SODm, specifically, EUK-134, a SODm with catalase activity, and tempol, a SODm with ROS-scavenging properties, on paraquat-induced nephrotoxicity of renal NRK-52E cells. Incubation with paraquat (1 mM) for 24 h reduced cell viability and increased necrosis significantly. Paraquat also generated significant quantities of superoxide anions and hydroxyl radicals. Both EUK-134 (10–300 μM) and tempol (0.3–1.0 mM) were able to improve cell viability and reduced paraquat-induced cell death significantly via dismutation or scavenging of superoxide anions and reduced hydroxyl radical generation. The data presented here suggest that SODm such as EUK-134 and tempol, which possess additional catalase and/or ROS-scavenging activities, can significantly reduce renal cell damage caused by paraquat. These effects were evident at concentrations which avoid the pro-oxidant activities associated with higher concentrations of SOD. Such SODm could therefore prove to be beneficial as therapies for paraquat nephrotoxicity.

Item Type: Journal article
Uncontrolled Keywords: EUK-134; Kidney; Nephrotoxicity; NRK-52E; Paraquat; Reactive oxygen species; Renal; Superoxide; Superoxide dismutase mimetic; Tempol; Free radicals
Subjects: C000 Biological and Biomedical Sciences
DOI (a stable link to the resource): 10.1016/j.freeradbiomed.2007.05.014
Faculties: Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences > Disease Process > Clinical Practice
Depositing User: editor spbs
Date Deposited: 08 Nov 2007
Last Modified: 04 Nov 2013 13:36
URI: http://eprints.brighton.ac.uk/id/eprint/2638

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