Pentoxifylline prevents the meglumine antimonate-induced renal toxicity in rats, but not that induced by the inorganic antimony pentachloride.
2008
Abstract Tumor necrosis factor-alpha (TNF-α) is a mediator of inflammation and has an important role in human and experimental renal diseases. Pentoxifylline (PTX) has been shown to inhibit cytokine synthesis, including TNF-α. The aim of the present study was to examine the effect of PTX on meglumine antimonate (Sb V ) and antimony pentachloride (SbCl 5 )-induced renal toxicity in rats. Sixty Wistar rats were divided into six groups according to the treatment employed over the period of 7 days: group I—saline (NaCl 0.9%); group II—PTX plus saline; group III—meglumine antimonate (Sb V ) plus saline; group IV—meglumine antimonate (Sb V ) plus PTX; group V—SbCl 5 plus saline; group VI—SbCl 5 with PTX. The animals’ urinary concentration ability was evaluated before and after the end of the treatment. Urine and blood osmolality, sodium and creatinine concentration, and urine volume per minute ( V ) were determined. Creatinine clearance (CrCl), fractional sodium excretion (FE Na ), and urine to plasma osmolality ratio (U/P osm) were calculated. TNF-α concentration in blood was assessed. On the seventh day, the animals were sacrificed and their kidneys were submitted to histological analysis. The meglumine antimonate (Sb V )-treated animals showed an impaired renal capacity to concentrate urine, with low values of the ratio U/P osm, reduction in CrCl, and an increment in TNF-α serum levels. PTX associated with meglumine antimonate (Sb V ) reduced TNF-α serum levels and was effective in preventing renal functional alterations. Rats treated with SbCl 5 showed functional and histopathologic alterations compatible with acute tubular necrosis, and treatment with PTX did not prevent SbCl 5 -induced nephrotoxicity. PTX was effective in preventing renal functional alterations induced by meglumine antimonate (Sb V ) in rats.
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