Elsevier

Pharmacological Research

Volume 46, Issue 4, October 2002, Pages 345-349
Pharmacological Research

EFFECTS OF TRIMETAZIDINE ON TISSUE DAMAGE IN KIDNEY AFTER HINDLIMB ISCHEMIA-REPERFUSION

https://doi.org/10.1016/S104366180200172XGet rights and content

Abstract

The objective of this study was to investigate the effects of trimetazidine (TMZ) on tissue damage in kidney after hindlimb ischemia-reperfusion (I/R), by assessing blood biochemical assay and histopathological analysis. Adult male Wistar rats were divided into two groups. TMZ 10 mg kg−1 day−1 was administrated twice a day for 10 days to the treatment group (group T, n=10). Sham group was given only 5% gum arabic (group S, n=10). On 11th day of treatment, 8 h I/R period was performed on right hindlimb of the rats. At the end of reperfusion period, a 5 ml blood withdrawn from ascending aorta for biochemical assays and their right kidneys were harvested for histopathological examination. Superoxide dismutase, Na+-K+ ATPase, and reduced glutathione levels were significantly increased in group T (P<0.001). On the other hand, myeloperoxidase and malondialdehyde levels were significantly less in group T than group S (P<0.001). Kidneys from the sham-operated group displayed intense leukocytic infiltration in histopathological examination.

These overall results strongly suggested that TMZ contributes renal protection from hindlimb I/R injury by decreasing systemic oxidative stress.

Section snippets

INTRODUCTION

Ischemia followed by reperfusion is a frequent clinical problem especially in cardiovascular surgery. Reperfusion injury is an inevitable consequence of the surgical intervention to relieve ischemia caused by acute arterial occlusion. Injury is not only limited to organs involved but also involve in distant organs [1].

Ischemia-reperfusion (I/R) of one organ, generate reactive oxygen species (ROS) such as superoxide anions, hydroxyl radicals, and hydrogen peroxides that can increase the systemic

Experimental protocol

Adult male Wistar rats weighing 250–300 g were used in this study. All animal procedures used are in strict accordance with the National Institutes of Health Guidelines on the Care and Use of Laboratory Animals, and approval of the ethics committee of Mersin University School of Medicine was obtained before study.

Animals were divided into two groups. TMZ 10 mg kg−1 day−1 was administrated by single gavage vehicle twice a day 8:00 a.m. and 18:00 p.m. for 10 days to treatment group (group T, n=10).

RESULTS

One animal died due to anesthesia complications in group T.

DISCUSSION

In this study, we herein demonstrated that I/R of the hindlimb caused distant organ injury as reflected by increased vascular permeability and hemorrhage in kidney. At the same time, I/R increased levels of MPO and MDA in systemic circulation suggesting neutrophil activation and lipid peroxidation, respectively. In accordance with these results SOD, Na+-K+ ATPase, and GSH levels were found to be decreased in group S.

It is well recognized that the I/R phenomenon is characterized by an increase

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