Selenium Attenuates Cholestasis-Induced Liver Injury and Fibrosis by Alleviating Liver Oxidative Stress and Inflammation in Rats

N. Nassef, Fatma M. Lebda, S. E. El Agaty, Marina Atef
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Abstract

Background: Oxidative stress and inflammation are primarily implicated in the development and progression of liver injury during cholestasis. Selenium, a known essential antioxidant trace element, was found to provide a remarkable antioxidant and anti-inflammatory effects on various diseases. Aim: This study was planned to evaluate the possible protective effect of selenium supplementation in a rat model of chronic cholestasis. Design: Experimental study. Methods: This study was carried out on adult male rats allocated randomly into sham, 4 weeks bile duct ligated (BDL), and BDLselenium treated (BDL-Se) groups. Sodium selenite was given by gavage daily, in a dose of 100 μg/kg for 6 weeks, starting 2 weeks before the BDL. Results: BDL group presented a significant increase in serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and liver levels of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1(TGF-β1), associated with a significant decrease in serum levels of total proteins (TP) compared to sham group . Selenium supplementation significantly lowered serum levels of AST, ALT, ALP, and liver levels of MDA, TNF-α, and TGF-β1, along with a significant increase in serum TP in BDL-Se group versus BDL rats. Histological analysis of liver showed a significant attenuation of the inflammatory score and a significant decrease in the percentage area of collagen deposition in BDL-Se group versus BDL rats. Conclusion: Selenium supplementation reduces liver injury and improves liver functions in experimental cholestasis probably by its antioxidant and antiinflammatory activities, which further alleviate the liver fibrosis.
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硒通过减轻肝脏氧化应激和炎症减轻胆汁淤积引起的肝损伤和纤维化
背景:氧化应激和炎症主要涉及胆汁淤积时肝损伤的发生和进展。硒是一种已知的必需抗氧化微量元素,对多种疾病具有显著的抗氧化和抗炎作用。目的:探讨硒对慢性胆汁淤积大鼠模型的保护作用。设计:实验研究。方法:以成年雄性大鼠为实验对象,随机分为假手术组、结扎4周胆管组(BDL)和胆总管硒治疗组(BDL- se)。亚硒酸钠每日灌胃,剂量为100 μg/kg,从BDL前2周开始,持续6周。结果:BDL组大鼠血清谷草转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)水平显著升高,肝脏丙二醛(MDA)、肿瘤坏死因子α (TNF-α)、转化生长因子β1 (TGF-β1)水平显著升高,血清总蛋白(TP)水平显著降低。与BDL大鼠相比,添加硒显著降低血清AST、ALT、ALP水平,降低肝脏MDA、TNF-α和TGF-β1水平,显著升高血清TP水平。肝脏组织学分析显示,与BDL大鼠相比,BDL- se组炎症评分明显降低,胶原沉积面积百分比明显减少。结论:硒可能通过其抗氧化和抗炎作用减轻实验性胆汁淤积肝损伤,改善肝功能,进一步减轻肝纤维化。
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