کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5829510 | 1558996 | 2012 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of cystathionine gamma-lyase and the biosynthesis of endogenous hydrogen sulphide ameliorates gentamicin-induced nephrotoxicity
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Clinical use of gentamicin over prolonged periods is limited because of dose- and time-dependent nephrotoxicity. Primarily, lysosomal phospholipidosis, intracellular oxidative stress and heightened inflammation have been implicated. Hydrogen sulphide is an endogenously produced signal transduction molecule with strong anti-inflammatory, anti-apoptotic and cytoprotective properties. In several models of inflammatory disease however, tissue damage has been associated with increased activity of cystathionine gamma-lyase, biosynthesis of hydrogen sulphide and activation of leukocytes. The aim of this study was to determine effects of inhibiting hydrogen sulphide biosynthesis by DL-propargyl glycine (an irreversible inhibitor of cystathionine gamma-lyase) on inflammation, necrosis and renal function, following treatment with gentamicin in rats. Adult female Sprague-Dawley rats were divided into six groups and treated with; physiological saline, sodium hydrosulphide, DL-propargyl glycine, gentamicin, a combination of gentamicin and sodium hydrosulphide, or gentamicin and DL-propargyl glycine respectively. Gentamicin-induced histopathological changes including inflammatory cell infiltration and tubular necrosis were attenuated by co-administering gentamicin with DL-propargyl glycine (PÂ <Â 0.05 compared to saline controls and PÂ <Â 0.05 compared to gentamicin only). Similarly, DL-propargyl glycine caused a significant reduction (PÂ <Â 0.05) in lipid peroxidation, production of superoxide and the activation of tumour necrosis factor-alpha in gentamicin-treated animals. These data show that protective effects of DL-propargyl glycine might be related at least in part, to the reduced inflammatory responses observed in animals treated with both gentamicin and DL-propargyl glycine. Thus, enzyme systems involved in hydrogen sulphide biosynthesis may offer a viable therapeutic target in alleviating the nephrotoxic effects of gentamicin.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 685, Issues 1â3, 15 June 2012, Pages 165-173
Journal: European Journal of Pharmacology - Volume 685, Issues 1â3, 15 June 2012, Pages 165-173
نویسندگان
Van P. Dam, Jennifer L. Scott, Anthony Ross, Robert T. Kinobe,