کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5559776 1561689 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The inhibition of inducible nitric oxide synthase and oxidative stress by agmatine attenuates vascular dysfunction in rat acute endotoxemic model
ترجمه فارسی عنوان
مهار سنتاز اکسید نیتریک اکسید و استرس اکسیداتیو توسط آگماتین باعث کاهش اختلال عملکرد عروق در مدل اندوتوکسیم حاد موش صحرایی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی


- Agmatine prevented LPS induced vascular hyporeactivity and endothelial dysfunction.
- Agmatine inhibited excessive NO production through inhibition of iNOS expression.
- Agmatine attenuated oxidative stress associating acute endotoxemia in rats.
- Agmatine is a safe endogenous metabolite with therapeutic potential in acute sepsis.

Vascular dysfunction leading to hypotension is a major complication in patients with septic shock. Inducible nitric oxide synthase (iNOS) together with oxidative stress play an important role in development of vascular dysfunction in sepsis. Searching for an endogenous, safe and yet effective remedy was the chief goal for this study. The current study investigated the effect of agmatine (AGM), an endogenous metabolite of l-arginine, on sepsis-induced vascular dysfunction induced by lipopolysaccharides (LPS) in rats. AGM pretreatment (10 mg/kg, i.v.) 1 h before LPS (5 mg/kg, i.v.) prevented the LPS-induced mortality and elevations in serum creatine kinase-MB isoenzyme (CK-MB) activity, lactate dehydrogenase (LDH) activity, C-reactive protein (CRP) level and total nitrite/nitrate (NOx) level after 24 h from LPS injection. The elevation in aortic lipid peroxidation illustrated by increased malondialdehyde (MDA) content and the decrease in aortic glutathione (GSH) and superoxide dismutase (SOD) were also ameliorated by AGM. Additionally, AGM prevented LPS-induced elevation in mRNA expression of iNOS, while endothelial NOS (eNOS) mRNA was not affected. Furthermore AGM prevented the impaired aortic contraction to KCl and phenylephrine (PE) and endothelium-dependent relaxation to acetylcholine (ACh) without affecting endothelium-independent relaxation to sodium nitroprusside (SNP). In conclusion: AGM may represent a potential endogenous therapeutic candidate for sepsis-induced vascular dysfunction through its inhibiting effect on iNOS expression and oxidative stress.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Environmental Toxicology and Pharmacology - Volume 55, October 2017, Pages 74-80
نویسندگان
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