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

Abstract

Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. Thus, the present study was undertaken to determine if pentoxifylline could protect the kidney in this experimental model. Thirty male Wistar rats were used. The animals were divided into three groups, each with 10 animals. The GM group of animals was treated daily with gentamicin in a dose of 100 mg/kg for eight days. The GMP group of animals was treated daily with pentoxifylline in a dose of 45 mg/kg and the same dose of gentamicin as the GM group for eight days. The control group received 1 mL/day saline intraperitoneally. For histological analysis, 5 μm-thick sections were stained with hematoxylin and eosin (HE), periodic acid Schiff (PAS), and Jones methenamine silver. The morphometric parameters included were glomerular area, major and minor axis, perimeter, diameter, roundness, and mean optical density. Biochemical analyses were used to determine concentrations of blood urea, serum creatinine, sodium, and potassium. In the GM group of rats, glomerular basement membrane was diffusely and unequally thickened with polymorphonuclear leukocyte infiltration, and coagulation-type necrosis and vacuolization of cytoplasm of proximal tubules epithelial cells were observed. In the GMP group of rats, glomeruli were slightly enlarged with thickened basement membrane in some segments but without coagulation-type necrosis of proximal tubules epithelial cells. Blood urea and serum creatinine concentration in the GM group were significantly elevated in comparison with the GMP group, while the potassium level was decreased. The present study indicated that pentoxifylline could provide a marked protective effect against gentamicin-induced acute renal failure, most likely mediated by vascular decongestion.

Pentoxifylline in Ischemia-Induced Acute Kidney Injury in Rats

“…On the other hand, Stojiljkovic et al [30] and Ozer et al [31] reported protective effects of pentoxifylline on aminoglycoside-induced nephrotoxicity, as assessed by serum creatinine and urea and histological analysis. It is conceivable that the mechanisms of protection provided by pentoxifylline against nephrotoxicity would not be operative in the pathogenesis of ischemia-induced renal injury.…”

Ameliorative effects of pentoxifylline on NOS induced by diabetes in rat kidney

“…27 Moreover, many studies have shown the beneficial effects of PTX in diabetic or nondiabetic kidney disease. It has been reported that PTX could provide an ameliorative effect against gentamicin, 9 cisplatin, 28 glycerol 29 and cyclosporine-induced nephrotoxicity. 30 In addition, PTX has shown beneficial effects in experimental models of DN and remnant kidney, with a reduction in renal hypertrophy, renal disease progression and urinary albumin excretion, 31 whereas clinical trials have demonstrated that PTF reduces clinical markers of glomerular and tubulointerstitial injury in diabetic subjects.…”

“…8 In addition, it has been used as an antioxidant in order to heal damage in several tissues. 9 Previous studies reported that PTX ameliorates the clinical markers of glomerular and tubulointerstitial injury in diabetic patients. 10 In addition, recently reported studies indicate that PTX may decrease proteinuria.…”

The Effect of Grape Seed Proanthocyanidin Extract in Preventing Amikacin-Induced Nephropathy

“…Gentamicin nephropathy models have been more extensively studied, using molecules including fish oil, 4 pentoxifylline, 5 green tea, 6 caffeic acid phenyl ester (CAPE), 7 vitamin E and vitamin C, 8 and GSPE, 11 (a) (A) and so on. The AK nephropathy model has been used in fewer studies, but the effects of antioxidant molecules including CAPE, 3 N-acetylcysteine (NAC), 9 melatonin, 22 and pentoxifylline 10 have been investigated.…”

“…4 Several experimental studies have been conducted in order to find a way to reduce AG-induced toxicity, and the effects of antioxidant molecules on reducing oxidative damage have been investigated in most of these studies. [3][4][5][6][7][8][9][10][11] It has been demonstrated that oxidative damage can be partially reduced by these drugs. However, there are as yet no molecules approved as an effective method to prevent AG nephropathy in clinical practice.…”