Effect of Vitamin E and Pentoxifylline on Glycerol-Induced Acute Renal Failure

Abstract

The pathogenesis of acute renal failure may involve, among other causes, ischemia, vascular congestion, arachidonic acid pathways, and reactive oxygen metabolites. The aim of this study is to evaluate the effects of pentoxifylline and vitamin E on the prevention of experimental acute renal failure induced by glycerol. Eighty-five Sprague-Dawley rats weighing 170–230 g were included in the study. The rats were randomly divided into four groups: group 1 was given 1 ml saline; group 2, glycerol; group 3, glycerol plus vitamin E, and group 4, glycerol plus pentoxifylline. Extent of histological renal tubular necrosis and regeneration in each animal were graded. Blood urea nitrogen, serum creatinine, and creatine kinase concentrations were measured. Mean blood urea nitrogen and serum creatinine concentrations and tubular injury scores were significantly lower in group 1 than in groups 2–4 (p < 0.001), but there were no significant differences among groups 2–4. We conclude that postinsult administration of vitamin E and pentoxifylline does not have a beneficial effect on prevention and severity of acute renal failure and that controlled, multicenter studies involving a large number of patients are needed to clarify this subject.

Protective Effects of Pentoxifylline Treatment on Gentamicin-Induced Nephrotoxicity in Rats

“…Applied alone or together with vitamin E pentoxifylline shows satisfactory effects on renal damage. [42,43] Glomeruli were insignificantly enlarged and the basement membrane of glomerular capillaries was thickened only in some segments of glomeruli. Pentoxifylline prevents the increased production of TNF-alpha, which induces apoptosis, [44] and other cytotoxins that are important factors of cellular proliferation and ECM synthesis of mesangial cells of glomeruli and interstitial fibroblasts.…”

“…Taken together, these data suggest that pentoxifylline exerts an ameliorative effect on the course of experimental ARF, which is in accordance with the results of other authors. [43,46,47] The mechanism of amelioration most likely involves the stimulation of renal vasodilator prostaglandins as well as the prevention of vascular congestion. [48] On the other hand, it has been shown that PTX affects calcium homeostasis and inhibits calcium entry in the human erythrocytes.…”

Protective effect of vitamin E against acute kidney injury

“…However, it was also reported by some scientists that a single vitamin E administration did not have a beneficial effect on the prevention and severity of AKI, as the oxidative stress in the kidney tissue could not be absolutely related to renal dysfunction in some AKI models [22,37]. Therefore, developing new therapy modes with vitamin E is essential for improving its therapeutic action against AKI as well as against other kidney diseases.…”

“…However, despite its well-documented antioxidant properties and other benefits, supplementation with vitamin E has failed to offer consistent benefits in some AKI models [22,37] as well as in some other diseases [55][56][57][58], as oxidative stress in tissues may not be absolutely related to the dysfunction. Therefore, a clear comprehension of the pathogenies of those diseases can reasonably guide the application of vitamin E in clinical research.…”

L-Citrulline Protects Against Glycerol-Induced Acute Renal Failure in Rats

“…2 The mechanisms of glycerol-induced myoglobinuric ARF are renal vasoconstriction and congestion, ischemia, and myoglobin-induced cytotoxicity. 3,4 Moreover, some studies show that the release of myoglobin lead to the increase of iron content in the plasma and the latter promotes free radical formation lipid peroxidation and renal dysfunction. 5,6 And there is growing evidence indicating that the reactive oxygen species (ROS) plays an important role in the pathogenesis of myoglobinuric ARF, oxidative stress would participate in the tubular necrosis favoring lipid peroxidation of cellular membranes.…”