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Protective effects of pentoxifylline treatment on gentamicin-induced nephrotoxicity in rats
Nenad Stojiljkovic1, Slavimir Veljkovic, Dragan Mihailovic
1Department of Physiology, University of Nis, School of Medicine, Nis, Serbia.
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 microm-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.
Insights
Pentoxifylline protects against gentamicin-induced kidney damage. This study shows pentoxifylline reduces acute renal failure caused by gentamicin, likely by improving blood flow in the kidneys.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Gentamicin (GM) is a critical antibiotic for severe infections.
- Gentamicin-induced nephrotoxicity limits its clinical use.
- Investigating protective agents against gentamicin nephrotoxicity is crucial.
Purpose of the Study:
- To evaluate the protective effect of pentoxifylline against gentamicin-induced nephrotoxicity in a rat model.
- To assess histological and biochemical markers of kidney damage.
Main Methods:
- Thirty male Wistar rats were divided into three groups: gentamicin (GM), gentamicin + pentoxifylline (GMP), and control.
- Animals received daily treatments for eight days.
- Histological (HE, PAS, Jones silver) and biochemical analyses (blood urea, creatinine, electrolytes) were performed.
Main Results:
- Gentamicin treatment led to glomerular basement membrane thickening, leukocyte infiltration, and proximal tubule necrosis.
- Pentoxifylline co-administration (GMP group) showed reduced histological damage compared to the GM group.
- Biochemical analysis revealed significantly elevated blood urea and serum creatinine in the GM group versus the GMP group, with decreased potassium in the GM group.
Conclusions:
- Pentoxifylline demonstrates a significant protective effect against gentamicin-induced acute renal failure in rats.
- The protective mechanism may involve mitigating vascular congestion.
- Pentoxifylline is a potential therapeutic agent to prevent gentamicin nephrotoxicity.
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