title: Pentoxifylline prevents the meglumine antimonate-induced renal toxicity in rats, but not that induced by the inorganic antimony pentachloride.
abstract: Tumor necrosis factor-alpha (TNF-alpha) 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-alpha. 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-alpha 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-alpha serum levels. PTX associated with meglumine antimonate (Sb(V)) reduced TNF-alpha 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.
authors.affiliation: Laboratory of Nephrology, Clinical Medicine, Faculty of Medicine, University of Brasilia, 70.910-900 Brasilia, DF, Brazil.
authors.forename: Flávio José Dutra
authors.initials: FJ
authors.lastname: de Moura
authors.forename: Pushkin Pires
authors.initials: PP
authors.lastname: Leal
authors.forename: Rogério
authors.initials: R
authors.lastname: de Souza Furtado
authors.forename: Maria Imaculada
authors.initials: MI
authors.lastname: Muniz-Junqueira
authors.forename: Joel Paulo Russomano
authors.initials: JP
authors.lastname: Veiga
mesh_terms: D000818:Animals; D000965:Antimony / Q000633:toxicity*; D000981:Antiprotozoal Agents / Q000633:toxicity*; D002712:Chlorides / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D007677:Kidney Function Tests; D007896:Leishmaniasis / Q000188:drug therapy; D008297:Male; D008536:Meglumine / Q000633:toxicity*; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000633:toxicity*; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000981:Antiprotozoal Agents; D002712:Chlorides; D009942:Organometallic Compounds; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C047841:antimony pentachloride; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000965:Antimony; D010431:Pentoxifylline