کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2580408 1561620 2014 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Resveratrol mitigate structural changes and hepatic stellate cell activation in N′-nitrosodimethylamine-induced liver fibrosis via restraining oxidative damage
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Resveratrol mitigate structural changes and hepatic stellate cell activation in N′-nitrosodimethylamine-induced liver fibrosis via restraining oxidative damage
چکیده انگلیسی
Resveratrol, a polyphenol, found in skin of red grapes, peanuts and berries possesses anti-inflammatory, anti-carcinogenic and lipid modulation properties. Here, we demonstrate in vivo antifibrotic activity of resveratrol in a mammalian model, wherein hepatic fibrosis was induced by N′-nitrosodimethylamine (NDMA) administration. Apart from being a potent hepatotoxin, NDMA is a known mutagen and carcinogen, as well. To induce hepatic fibrosis, rats were administered NDMA (i.p.) in 10 mg/kg b.wt thrice/week for 21 days. Another group of animals received resveratrol supplement (10 mg/kg b.wt) subsequent to NDMA administration and were sacrificed weekly. The changes in selected biomarkers were monitored to compare profibrotic effects of NDMA and antifibrotic activity of resveratrol. The selected biomarkers were: sera transaminases, ALP, bilirubin, liver glycogen, LPO, SOD, protein carbonyl content, ATPases (Ca2+, Mg2+, Na+/K+) and hydroxyproline/collagen content. Alterations in liver architecture were assessed by H&E, Masson's trichrome and reticulin staining of liver biopsies. Immuno-histochemistry and immunoblotting were employed to examine expression of α-SMA. Our results demonstrate that during NDMA-induced liver fibrosis transaminases, ALP, bilirubin, hydroxyproline and liver collagen increases, while liver glycogen is depleted. The decline in SOD (>65%) and ATPases, which were concomitant with the elevation in MDA and protein carbonyls, strongly indicate oxidative damage. Fibrotic transformation of liver in NDMA-treated rats was verified by histopathology, immuno-histochemistry and immunoblotting data, with the higher expressivity of α-SMA-positive HSCs being most established diagnostic immuno-histochemical marker of HSCs. Resveratrol-supplement refurbished liver architecture by significantly restoring levels of biomarkers of oxidative damage (MDA, SOD, protein carbonyls and membrane-bound ATPases). Therefore, we conclude that antifibrotic effect of resveratrol is due to restrained oxidative damage and down-regulation of α-SMA, which inhibits HSC activation to obstruct liver fibrosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 221, 25 September 2014, Pages 1-12
نویسندگان
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