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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 5(1)-nucleotidase (5(1)-NTD) enzymes as well as gamma-glutamyltransferase (gamma-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 gamma-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.

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  • Authors+Show Affiliations

    ,

    Department of Biochemistry, Drug Metabolism and Toxicology Unit, University of Ibadan, Ibadan, Nigeria.

    ,

    Source

    Fundamental & clinical pharmacology 20:3 2006 Jun pg 263-71

    MeSH

    Animals
    Antioxidants
    Aspartate Aminotransferases
    Catalase
    Disease Models, Animal
    Dose-Response Relationship, Drug
    Gentamicins
    Glutathione
    Glutathione Transferase
    Kidney
    Kidney Tubules, Proximal
    Necrosis
    Phenols
    Plant Extracts
    Rats
    Rats, Wistar
    Renal Insufficiency
    Soybeans
    Superoxide Dismutase
    gamma-Glutamyltransferase

    Pub Type(s)

    Comparative Study
    Journal Article

    Language

    eng

    PubMed ID

    16671961

    Citation

    TY - JOUR T1 - Modulation of gentamicin-induced renal dysfunction and injury by the phenolic extract of soybean (Glycine max). AU - Ekor,Martins, AU - Farombi,Ebenezer Olatunde, AU - Emerole,Godwin O, PY - 2006/5/5/pubmed PY - 2006/12/19/medline PY - 2006/5/5/entrez SP - 263 EP - 71 JF - Fundamental & clinical pharmacology JO - Fundam Clin Pharmacol VL - 20 IS - 3 N2 - 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 5(1)-nucleotidase (5(1)-NTD) enzymes as well as gamma-glutamyltransferase (gamma-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 gamma-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. SN - 0767-3981 UR - https://www.unboundmedicine.com/medline/citation/16671961/Modulation_of_gentamicin_induced_renal_dysfunction_and_injury_by_the_phenolic_extract_of_soybean__Glycine_max__ L2 - http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0767-3981&date=2006&volume=20&issue=3&spage=263 ER -