کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9034502 1132617 2005 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Sodium benzoate attenuates d-serine induced nephrotoxicity in the rat
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Sodium benzoate attenuates d-serine induced nephrotoxicity in the rat
چکیده انگلیسی
d-Serine causes selective necrosis to the straight portion of the rat renal proximal tubules. The onset is rapid, occurring within 3-4 h and accompanied by proteinuria, glucosuria and aminoaciduria. The metabolism of d-serine by d-amino acid oxidase (d-AAO) may be involved in the mechanism of toxicity. d-AAO is localized within the peroxisomes of renal tubular epithelial cells, which is also the location of d-serine reabsorption. To address the role of d-AAO in d-serine-induced nephrotoxicity, we have examined the effect of sodium benzoate (SB) on the renal injury. SB has been shown to be a potent, competitive inhibitor of kidney d-AAO in vitro. Male Alderley Park rats were exposed to d-serine (500 mg/kg ip) 1 h after exposure to SB (125, 250, 500 or 750 mg/kg ip). Urine was collected for 0-6 h, then terminal plasma samples and kidneys were taken at 6.5 h. A second group of animals was given SB (500 mg/kg) followed by d-serine (500 mg/kg ip; 1 h later) and urine was collected after 0-6, 6-24 and 24-48 h. Terminal plasma samples and kidneys were taken at 48 h. 1H NMR spectroscopic analysis of urine, combined with principal component analysis, demonstrated that SB was able to prevent d-serine-induced perturbations to the urinary profile in a dose dependent manner. This was confirmed by measurement of plasma creatinine and urinary glucose and protein and histopathological examination of the kidneys. Assessment 48 h after d-serine administration revealed that nephrotoxicity was observed in animals pre-treated with SB (500 mg/kg) although the extent of injury was less pronounced than following d-serine alone. These results demonstrate that whilst prior exposure to SB prevents the initial onset of d-serine-induced nephrotoxicity, renal injury is still apparent at later time points. d-AAO activity in the kidney was decreased by 50% 1 h after dosing with SB suggesting that inhibition of this enzyme may be responsible for the observed protection.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 207, Issue 1, 1 February 2005, Pages 35-48
نویسندگان
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