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β-胡萝卜素作为一种保护剂,通过生化方法对抗炎症、抗氧化和抗细胞凋亡,以防止溴苯诱发雌性 Wistar 白化大鼠的肝毒性。

A biochemical approach to the anti-inflammatory, antioxidant and antiapoptotic potential of beta-carotene as a protective agent against bromobenzene-induced hepatotoxicity in female Wistar albino rats.

机构信息

Vellore Institute of Technology, School of Bio Sciences and Technology, Vellore, India.

Kristu Jayanti College (Autonomous), Bengaluru, India.

出版信息

J Appl Biomed. 2020 Aug;18(2-3):87-95. doi: 10.32725/jab.2020.011. Epub 2020 Aug 10.

Abstract

Bromobenzene is a compound which has contributed much in understanding the mechanisms involved in xenobiotic hepatotoxicity induced by drugs and environment pollutants. In the present study, the protective and ameliorative effect of beta-carotene was investigated against bromobenzene-induced hepatotoxicity and compared with silymarin, a standard hepatoprotective reference drug. Beta-carotene (10 mg/kg b.w. p.o.) was administered to the rats for 9 days before intragastric intubation of bromobenzene (10 mmol/kg b.w.). Liver marker enzymes (aspartate transaminase, alanine transaminase and alkaline phosphatase), total protein content, bilirubin, total cholesterol, high-density lipoproteins, triglycerides, antioxidant status (reduced glutathione, superoxide dismutase, catalase, glutathione-S-transferase and glutathione peroxidase) were assessed along with histopathological analysis. ELISA was performed for analysing the levels of cytokines such as TNF-α, IL-1β and IL-6 in serum and in the liver. Caspase-3, COX-2 and NF-κB were evaluated by Western blotting. Administration of bromobenzene resulted in elevated levels of liver marker enzymes, bilirubin, lipid peroxidation and cytokines but deterioration in total protein content, antioxidant levels and histopathological conditions. Pre-treatment with beta-carotene not only significantly decreased the levels of liver markers, lipid peroxidation and cytokines but also improved histo-architecture and increased antioxidant levels minimising oxidative stress, and reduced factors contributing to apoptosis. This significant reversal of the biochemical changes on pre-treatment with beta-carotene in comparison with rats administered with bromobenzene clearly demonstrates that beta-carotene possesses promising hepatoprotective effect through its antioxidant, anti-inflammatory and antiapoptotic activity and hence is suggested as a potential therapeutic agent for protection from bromobenzene.

摘要

溴苯是一种化合物,它为理解药物和环境污染物引起的异生物质肝毒性的机制做出了重要贡献。在本研究中,研究了β-胡萝卜素对溴苯诱导的肝毒性的保护和改善作用,并与标准肝保护参考药物水飞蓟素进行了比较。β-胡萝卜素(10mg/kg b.w. 口服)在大鼠灌胃溴苯(10mmol/kg b.w.)前 9 天给予。评估了肝标志物酶(天门冬氨酸转氨酶、丙氨酸转氨酶和碱性磷酸酶)、总蛋白含量、胆红素、总胆固醇、高密度脂蛋白、甘油三酯、抗氧化状态(还原型谷胱甘肽、超氧化物歧化酶、过氧化氢酶、谷胱甘肽-S-转移酶和谷胱甘肽过氧化物酶)以及组织病理学分析。通过酶联免疫吸附测定(ELISA)分析血清和肝脏中细胞因子(TNF-α、IL-1β和 IL-6)的水平。通过 Western 印迹评估 caspase-3、COX-2 和 NF-κB。溴苯的给药导致肝标志物酶、胆红素、脂质过氧化和细胞因子水平升高,但总蛋白含量、抗氧化水平和组织病理学状况恶化。β-胡萝卜素预处理不仅显著降低了肝标志物、脂质过氧化和细胞因子的水平,而且改善了组织形态结构,增加了抗氧化水平,最大限度地减少了氧化应激,并减少了导致细胞凋亡的因素。与给予溴苯的大鼠相比,β-胡萝卜素预处理对生化变化的显著逆转清楚地表明,β-胡萝卜素通过其抗氧化、抗炎和抗凋亡活性具有有前途的肝保护作用,因此被建议作为保护免受溴苯的潜在治疗剂。

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