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Vinpocetine attenuates thioacetamide-induced liver fibrosis in rats.
Human & Experimental Toxicology ( IF 2.7 ) Pub Date : 2020-08-25 , DOI: 10.1177/0960327120947453
Ahmed A Elnfarawy 1 , Asmaa E Nashy 1 , Alaa M Abozaid 1 , Ibrahim F Komber 1 , Rawan H Elweshahy 1 , Rehab S Abdelrahman 2, 3
Affiliation  

Liver fibrosis is associated with increased mortality and morbidity. However, there is not effective treatment so far. Vinpocetine (Vinpo) is a synthetic derivative of vinca alkaloid vincamine. Limited previous reports have shown some beneficial effects of Vinpo in different organ fibrosis, but the ability of Vinpo to inhibit liver fibrosis induced by thioacetamide (TAA) has not been reported, that is why we investigate the potential ability of this vinca alkaloid derivative to attenuate liver fibrosis. Hepatic fibrosis was induced in male Sprague Dawley rats by TAA (200 mg/kg; ip; 3 times/week) for 6 weeks. Daily treatments with Vinpo (10–20 mg/kg/day; orally) ameliorated TAA-induced hepatic oxidative stress and histopathological damage as indicated by a decrease in liver injury markers, LDH, hepatic MDA, and NOx levels, as well as increase anti-oxidative parameters. Besides, the anti-fibrotic efficacy of Vinpo was confirmed by decreasing hydroxyproline, and α-SMA. Also, the anti-inflammatory effect of Vinpo was explored by decreasing IL-6 and TNF-α levels. Our novel findings were that Vinpo decreased VEGF/Ki-67 expression in the liver confirming its effect on angiogenesis and proliferation. These findings reveal the anti-fibrotic effect of Vinpo against TAA-induced liver fibrosis in rats, and suggest the modulation of oxidative stress, inflammation, angiogenesis and proliferation as mechanistic cassette underlines this effect.



中文翻译:


长春西汀可减轻硫代乙酰胺诱导的大鼠肝纤维化。



肝纤维化与死亡率和发病率增加有关。然而,迄今为止尚无有效的治疗方法。长春西汀(Vinpo)是长春花生物碱长春胺的合成衍生物。之前有限的报道显示了 Vinpo 对不同器官纤维化的一些有益作用,但 Vinpo 抑制硫代乙酰胺 (TAA) 诱导的肝纤维化的能力尚未报道,这就是为什么我们研究这种长春花生物碱衍生物的潜在减弱能力肝纤维化。通过TAA(200 mg/kg;腹腔注射;每周3次)诱导雄性Sprague Dawley大鼠肝纤维化,持续6周。每日用 Vinpo 治疗(10-20 mg/kg/天;口服)可改善 TAA 诱导的肝氧化应激和组织病理学损伤,肝损伤标记物、LDH、肝 MDA 和 NOx 水平降低,并增加抗氧化应激水平。 -氧化参数。此外,Vinpo 的抗纤维化功效通过降低羟脯氨酸和 α-SMA 得到证实。此外,还通过降低 IL-6 和 TNF-α 水平探索了 Vinpo 的抗炎作用。我们的新发现是 Vinpo 降低了肝脏中 VEGF/Ki-67 的表达,证实了它对血管生成和增殖的影响。这些发现揭示了 Vinpo 对 TAA 诱导的大鼠肝纤维化的抗纤维化作用,并表明氧化应激、炎症、血管生成和增殖的调节作为机制盒强调了这种作用。

更新日期:2020-08-25
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