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A study of oxidative stress in gentamicin induced nephrotoxicity and effect of antioxidant vitamin C in Wistar rats.

Chetankumar R. Acharya, Hetal N. Thakar, S. K. Vajpeyee.




Abstract

Background: Gentamicin is very useful aminoglycoside in treatment of gram negative organisms but nephrotoxicity has been a major limiting factor. Various renal pathologies have shown correlation with generation of oxidative stress. So, it was hypothesized that there may be involvement of oxidative stress in gentamicin nephrotoxicity.

Aims & Objective: To investigate the role of oxidative stress in gentamicin-induced nephrotoxicity and its prevention by using antioxidant vitamin C in Wistar albino rats. Another objective was to localize the site of kidney damage produced by gentamicin.

Materials and Methods: Male Wistar albino rats were administered gentamicin at the dose of 70 mg/kg/day i.m; either alone or in combination with vitamin C. Parameters of oxidative stress like glutathione peroxidase (GPx), glutathione reductase (GR) and total antioxidant status (TAS) were analysed. Renal damage was measured by blood urea and serum creatinine. Histopathological examination of rat kidney was
done. The data was subjected to one way ANOVA with post hoc test of significance and the values of P < 0.05 were considered statistically significant.

Results: Treatment with gentamicin caused significant reduction of TAS, GPx and GR activity, while blood urea and serum creatinine level were raised significantly as compared to control. Renal damage was confirmed with histopathological studies. The primary site of damage was identified as tubules especially proximal convoluted tubules. Administration of vitamin C alone raised TAS level significantly. Co-administration of vitamin C along with gentamicin led to significant restoration of GPx, GR, TAS, blood urea and serum creatinine level.

Conclusion: Renal damage due to gentamicin is associated with oxidative stress. The primary site of damage was renal proximal convoluted tubules. Co-administration of vitamin C along with gentamicin significantly prevented nephrotoxicity by virtue of its antioxidant effect.

Key words: Gentamicin, Nephrotoxicity, Vitamin C, Glutathione Peroxidase, Glutathione Reductase, Total Antioxidant status






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