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Nephrol Dial Transplant. 2006 Aug;21(8):2085-95. Epub 2006 May 16.

Protective role of L-2-oxothiazolidine-4-carboxylic acid in cisplatin-induced renal injury.

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  • 1Department of Internal Medicine, Chonbuk National University Medical School, 634-18, Keum-Am Dong, Jeonju 561-712, Republic of Korea.

Abstract

BACKGROUND:

Oxidative stress and inflammation are implicated in the pathogenesis of cisplatin-induced nephrotoxicity. l-2-oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrug, and increases cellular glutathione (GSH). OTC is converted to cysteine by the intracellular enzyme, oxoprolinase. To date, the protective role of OTC on cisplatin-induced renal injury has not been investigated. The purpose of the present study was to examine the protective effect of OTC on cisplatin-induced renal injury and to examine the mechanism of its protection.

METHODS:

Mice were treated with cisplatin with or without administration of OTC. The generation of reactive oxygen species (ROS), expression of intercellular adhesion molecule (ICAM)-1 and monocyte chemoattractant protein (MCP)-1 were determined in the kidney using 2',7'-dichlorofluorescein diacetate, immunostaining or western blot analysis. Nuclear factor (NF)-kappaB activity, infiltration of F4/80-positive cells and apoptosis were also investigated in addition to renal function and histology using electrophoretic mobility shift assay, immunostaining, western blot analysis, uridine triphosphate (dUTP) nick-end labelling or periodic acid-Schiff staining. The effect of OTC on superoxide dismutase activity and GSH level in cisplatin-treated normal adult human kidney (HK-2) cells were measured using assay kits.

RESULTS:

The administration of OTC resulted in a significant reduction of cisplatin-induced ROS production, the p65 subunit of NF-kappaB translocation into nucleus, expression of ICAM-1, caspase 3 activity, expression of MCP-1 and the infiltration of macrophages into renal tissue. OTC markedly ameliorated renal damage induced by cisplatin through antioxidant and anti-inflammatory effect.

CONCLUSIONS:

These results suggest that OTC can be a potential therapeutic agent in cisplatin-induced renal injury through decreasing the ROS levels and activation of NF-kappaB.

PMID:
16705027
[PubMed - indexed for MEDLINE]
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