کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9001652 | 1118542 | 2005 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibitors of calpain activation (PD150606 and E-64) and renal ischemia-reperfusion injury
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کلمات کلیدی
PMNPD150606E-64I-RARFMDANAGICAM-1NF-κBMPO - DFON-acetyl-β-d-glucosaminidase - N-acetyl-β-d-glycosaminidaseReperfusion-injury - آسیب مجددIschemia - ایسکمیischemia-reperfusion - ایسکمی-رپرفیوژنFeNa - بدnuclear factor-kappaB - فاکتور هسته ای - kappaBpolymorphonuclear leukocyte - لکوسیت پلی مرفون هسته ایmalondialdehyde - مالون دی آلدهیدCalpain inhibitor - مهار کننده کالپایینintercellular adhesion molecule-1 - مولکول چسبندگی بین سلولی -1myeloperoxidase - میلوپراکسیداز Acute renal failure - نارسایی حاد کلیه
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Calpain activation has been implicated in the development of ischemia-reperfusion (I-R) injury. Here we investigate the effects of two inhibitors of calpain activity, PD150606 and E-64, on the renal dysfunction and injury caused by I-R of rat kidneys in vivo. Male Wistar rats were administered PD150606 or E-64 (3 mg/kg i.p.) or vehicle (10%, v/v, DMSO) 30 min prior to I-R. Rats were subjected to bilateral renal ischemia (45 min) followed by reperfusion (6 h). Serum and urinary biochemical indicators of renal dysfunction and injury were measured; serum creatinine (for glomerular dysfunction), fractional excretion of Na+ (FENa, for tubular dysfunction) and urinary N-acetyl-β-d-glucosaminidase (NAG, for tubular injury). Additionally, kidney tissues were used for histological analysis of renal injury, immunohistochemical analysis of intercellular adhesion molecule-1 (ICAM-1) expression and nitrotyrosine formation. Renal myeloperoxidase (MPO) activity (for polymorphonuclear leukocyte infiltration) and malondialdehyde (MDA) levels (for tissue lipid peroxidation) were determined. Both PD150606 and E-64 significantly reduced the increases in serum creatinine, FENa and NAG caused by renal I-R, indicating attenuation of renal dysfunction and injury and reduced histological evidence of renal damage caused by I-R. Both PD150606 and E-64 markedly reduced the evidence of oxidative stress (ICAM-1 expression, MPO activity, MDA levels) and nitrosative stress (nitrotyrosine formation) in rat kidneys subjected to I-R. These findings provide the first evidence that calpain inhibitors can reduce the renal dysfunction and injury caused by I-R of the kidney and may be useful in enhancing the tolerance of the kidney against renal injury associated with aortovascular surgery or renal transplantation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 69, Issue 7, 1 April 2005, Pages 1121-1131
Journal: Biochemical Pharmacology - Volume 69, Issue 7, 1 April 2005, Pages 1121-1131
نویسندگان
Prabal K. Chatterjee, Zoran Todorovic, Ahila Sivarajah, Helder Mota-Filipe, Paul A.J. Brown, Keith N. Stewart, Emanuela Mazzon, Salvatore Cuzzocrea, Christoph Thiemermann,