Abstract

Problem statement: The Amino glycoside antibiotics cause drug induced nephrotoxicity at therapeutic doses and thus limits the use clinicall y. Oxidative stress is one of the main reasons for the development of nephrotoxicity. Approach: In light of this the aim of the present study was to investigate the role of mitochondrial as well as po st-mitochondrial oxidative stress in the developmen t of Gentamicin (GM) induced nephrotoxicity and to elucidate the role of Enicostemma Littoral blame (EL) extract, as a promising antioxidant therapy. R ats were divided into four groups, 1) (Control 2) GM (i.p., 80 mg kg -1 day -1 for 8 days) (treated 3) GM+EL treated (i.g, 2.5 gm kg -1 day -1 ) and (4) GM+ Vitamin C (VC) treated (i.g, 600 mg kg -1 day -1 ). GM treated animals showed high oxidative stress in mitochondrial as well as post-mitochondri al fractions of renal tissues as evidenced by increased lipid per oxidation levels, decrease in G SH content and activities of antioxidant enzymes, SOD and GPx. Results: Oxidative stress was more pronounced in mitochondrial fraction as compared to post-mitochondrial fraction. GM-induced nephrotoxicity was further corroborated by an increase in serum cretonne and Blood Urea Nitrogen (BUN) levels and altered kidney histopathological observations. Treatment with EL ameliorates antioxi dant defense system of mitochondrial as well as post-mitochondrial fraction, with better improvemen t seen in mitochondrial fraction. Conclusion: The present study explored beneficial effect of EL extr act as an antioxidant therapy to counteract mitochondrial and post-mitochondrial oxidative stre ss generated in kidney upon GM-treatment, thus prevented nephrotoxicity.

Highlights

  • Amino glycoside antibiotics, especially Gentamicin (GM) are widely applied in veterinary and human clinical practices for treatment of lifethreatening gram negative infections

  • Especially Gentamicin (GM) are widely applied in veterinary and human clinical practices for treatment of lifethreatening gram negative infections. These Aminoglycoside antibiotics cause drug induced the development of nephrotoxicity

  • Serum creatinine and urea: Serum creatinine level increased by 368% and Blood Urea Nitrogen level (BUN) increased by 176% in the GM group compared to the control (C) group (Table 2)

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Summary

INTRODUCTION

Especially Gentamicin (GM) are widely applied in veterinary and human clinical practices for treatment of lifethreatening gram negative infections These Aminoglycoside antibiotics cause drug induced the development of nephrotoxicity. Apart acute renal failure and to test the protective effects of from antidiabetic potential, we exhibited vitro antichemical compounds, plant extracts or drugs GM- malarial activity of methanolic extract of plant and induced nephrotoxicity is an ideal model (Ali and swertiamarin isolated from it (Soni and Gupta, 2009). Aqueous extract of EL has shown effect on key carbohydrate metabolic enzymes in alloxan-induced diabetic rats (Srinivasan et al, 2005) and in vitro antioxidant activity (Vaijanathappa and Badami, 2009). Extract in alloxan-induced diabetic rats (Vijayvargia et al, 2000; Maroo et al, 2002; 2003a; 2003b) and

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