Modulation of gentamicin-induced renal dysfunction and injury by the phenolic extract of soybean (Glycine max)

Abstract

Gentamicin (GM) is one of the most important of the aminoglycoside antibiotics used widely for the treatment of serious and life-threatening infections and whose clinical use is limited by its nephrotoxicity. As the pathogenesis of GM-induced renal dysfunction and injury involves reactive oxygen species, the polyphenolic constituents of soybean with antioxidant property may protect against GM-induced renal toxicity. We therefore tested this hypothesis using phenolic extract of soybean (PESB) on GM-induced nephrotoxicity rat model. Administration of GM (80 mg/kg, s.c.) for 12 days to rats induced marked renal failure, characterized by a significantly increased plasma creatinine, urea and Na+ ions levels, with K+ depletion. This was also associated with decreases in the activity of the renal antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST)] measured and depletion of both blood and renal reduced glutathione (GSH) levels. The activities of membrane-bound glucose-6-phosphatase (G6Pase) and 51-nucleotidase (51-NTD) enzymes as well as c-glutamyltransferase (c-GT) and aspartate aminotransferase (AST) (enzymes that are located in the proximal tubule) were decreased. Renal histology examination further confirmed the damage to the kidney as it reveals severe necrosis of the proximal renal tubules with deposition of colloid casts. These alterations were ameliorated in rats pretreated with PESB. The decrease in the activities of SOD, CAT, GST as well as GSH depletion observed in GM-treated rats was prevented in the rats pretreated with PESB. The activities of c-GT, AST and G6Pase were also increased in the kidney. These protective effects were dose dependent except for G6Pase activity and GSH levels that were preserved only at 500 mg/kg dose of PESB, and 5¢-NTD activity that was dose dependently decreased. Furthermore, the extent of tubular damage induced by GM was reduced in rats that also received PESB. The lower dose (500 mg/kg) of the extract, however, appeared to provide better histological protection. These results suggest that the PESB has protective effects on GM-mediated nephropathy and this may be related to the action of the antioxidant polyphenolic content of the soybean.