Protektivni efekti selena i salicilne kiseline kod pacova sa akutnom insuficijencijom bubrega izazvanom gentamicinom

Abstract

Gentamicin is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. Salicylic acid is a phenolic compound present in plants with free radical-scavenging and iron chelation properties. It is a hydroxyl radical scavenger and can affect the activation of transcription factors. Selenium is a fundamental trace element that plays an important role in a number of physiological processes, including the elimination of reactive oxygen species. The present study was designed to determine the protective effect of selenium and salicylic acid in gentamicin-induced nephrotoxicity in rats. Experiments were done on 64 adult Wistar rats divided into 8 groups of 8 animals each. The control group received only saline (1 ml/day) intraperitoneally (i.p.). Animals in the SE, SAL and SS groups, serving as positive controls, received only selenium (1 mg/kg), salicylic acid (100 mg/kg) and their combination, respectively. The GM group received gentamicin (100 mg/kg) i.p. The GSE group received the same dose of GM and selenium (1 mg/kg) by i.p. injections on a daily basis. The GSAL group received the same dose of GM and salicylic acid (100 mg/kg). The animals in GSS group received gentamicin with selenium and salicylic acid. All groups were treated during 8 consecutive days. Quantitative evaluation of GM-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological, biochemical and morphometric analyses in order to determine potential beneficial effects of selenium or salicylic acid coadministration with GM. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde levels and protein carbonyl groups indicated that gentamicin-induced tissue injury was mediated through oxidative reactions. Ultrastrucural changes in kidney after gentamicin treatment included enlargement of glomeruli, infiltration of mononuclear cells, rupture of the basal membrane and necrosis of tubular cells. Selenium and salicylic acid administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by gentamicin treatment. The results from our study indicate that selenium and salicylic acid attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats. Selenium and salicylic acid pretreatment results in significant reduction of morphological and functional kidney alterations induced by gentamicin.