Effects of co‐supplementation of vitamins E and C on gentamicin‐induced nephrotoxicity in rat

Abstract

Gentamicin (GM) is an effective antibiotic against severe gram-negative infections. However it can produce nephrotoxicity in human. Reactive oxygen species (ROS) have been proposed as the causative factors of the renal side effects the drug. This study was performed to investigate the protective role of antioxidant vitamins against GM-mediated nephropathy in an in situ model of isolated rat kidney. Male Sprague-Dawley rats were randomly assigned to one of the following groups of seven rats: group 1 (Control) was perfused with Tyrode solution; group 2 (GM), 200 µg ml −1 GM was added to the perfusate; group 3 (GM + Vit C), as group 2 with vitamin C added to the drinking water for 3 days (200 mg l −1 ) and to the perfusate (100 mg l −1 ); group 4 (GM + Vit E), as group 2 with vitamin E (100 mg (100 g body weight)−1 , I.M.) injected 12 h before the start of the experiment; group 5 (GM + Vit C + Vit E) as group 2 with vitamin E and C co-administered (concentrations and conditions as in groups 3 and 4). To compare the groups, urinary lactate dehydrogenase (LDH), N -acetyle-β-D-glucosaminidase (NAG) and alkaline phosphatase (ALP) activities, inulin clearance (glomerular filtration rate, GFR) and renal tissue glutathione (GSH) content were measured. GM caused a significant nephrotoxicity demonstrated by an increase in urinary LDH, NAG and ALP activities. Reduction in GSH content and a marked decrease in GFR were observed compared to controls. Vitamin C inhibited the GM-induced increase in urinary enzyme activities but did not show a significant effect on the GSH content or GFR. Vitamin E prevented the GM-induced reduction in GSH lelvel without a significant improvement in GFR. Co-administration of vitamins C and E significantly prevented the GM-induced nephrotoxicity demonstrating by preservation of GFR and GSH levels and prevention of increase in urinary enzyme activities. We conclude that co-administration of moderate doses of vitamins C and E has beneficial effects on renal preservation in GM-induced nephrotoxicity.

Protective Effect of Quercetin against Gentamicin-Induced Nephrotoxicity in Rats

“…It has been shown that GM exerts its adverse renal effect by generation of ROS 37) which results in sever tissue damage. 38) Under normal conditions, ROS, which are generated during cellular functions, are eliminated by intrinsic antioxidant enzyme systems like superoxide dismutase, catalase and glutathione peroxidase.…”

Erythropoietin ameliorates genetamicin-induced renal toxicity: A biochemical and histopathological study

“…Furthermore, ATP depletion from either mitochondrial damage or direct inhibition of mitochondrial oxidative phosphorylation (17-21) and reactive oxygen species (ROS) production are other mechanism take part in nephrotoxicity (18)(19)(20). Most studies reported previously were designed to administer drugs before or at the same time of renal insult (18)(19)(20)(21)(22)(23)(24). However, most therapeutic agents are usually administered after the expression of clinical diseases.…”

Erythropoietin; bright future and new hopes for an old drug

“…However, it has some nephrotoxicity which causes limitations in the extent of its use. In recent years there have been many studies on the mechanisms of GM-induced nephrotoxicity and reduction of the renal damage caused by it (3,4). issue of journal, the effects of erythropoietin on amelioration of gentamicin-induced renal toxicity was investigated by biochemical and histopathological indices (5).…”