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大鼠中抗肝损伤相关肝毒性和氧化损伤的药代动力学及治疗潜力:计算、生化和组织学研究

Pharmacokinetics and Therapeutic Potential of against Liver Damage Associated Hepatotoxicity and Oxidative Injury in Rats: Computational, Biochemical and Histological Studies.

作者信息

Rahmouni Fatma, Badraoui Riadh, Ben-Nasr Hmed, Bardakci Fevzi, Elkahoui Salem, Siddiqui Arif J, Saeed Mohd, Snoussi Mejdi, Saoudi Mongi, Rebai Tarek

机构信息

Laboratory of Histo-Embryology and Cytogenetics, Medicine Faculty of Sfax, University of Sfax, Sfax 3029, Tunisia.

Department of Biology, College of Science, University of Ha'il, Ha'il 81451, Saudi Arabia.

出版信息

Life (Basel). 2022 Jul 21;12(7):1092. doi: 10.3390/life12071092.

Abstract

This study investigated the druggability, pharmacokinetics and ethyl acetate extract of (EA ) and the protective effect against carbon tetrachloride (CCl) induced liver cirrhosis in rats. The total antioxidant capacity (TAC) and scavenging activity of the extract were examined. The in vivo protective study was based on the use of an animal model of CCl-induced liver cirrhosis. Four groups of rats have been used: Group I: control rats; Group II: received CCl in olive oil (0.5 mL/kg); Group III: received the EA (25 mg/kg) of pretreatment for seven days by gavage then CCl in olive oil by gavage for 15 days. Group IV: received the EA of for seven days (25 mg/kg). EA was found to possess significant antioxidant capacity. CCl caused a hepatotoxicity associated increase in both levels of AST and ALT, which were reduced back to normal values following EA pretreatment. Hepatotoxicity associated structural modifications of liver tissues and increase in thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and carbonyl proteins (CP), associated decreases in several assessed antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). The in vivo findings on the protective effect of were supported by its druggability, its pharmacokinetic properties and molecular docking assays. These results confirm the modulatory antioxidant and hepatoprotective potential of in this experimental liver cirrhosis model. phytochemicals are good candidates for further pharmaceutical explorations and drug design.

摘要

本研究调查了[具体物质名称未给出]的可药用性、药代动力学以及乙酸乙酯提取物(EA)对四氯化碳(CCl₄)诱导的大鼠肝硬化的保护作用。检测了提取物的总抗氧化能力(TAC)和清除活性。体内保护研究基于使用CCl₄诱导的肝硬化动物模型。使用了四组大鼠:第一组:对照大鼠;第二组:接受橄榄油中CCl₄(0.5 mL/kg);第三组:通过灌胃预处理7天给予EA(25 mg/kg),然后通过灌胃给予橄榄油中的CCl₄ 15天。第四组:接受EA(25 mg/kg)7天。发现EA具有显著的抗氧化能力。CCl₄导致肝毒性,伴随AST和ALT水平升高,而EA预处理后这些水平恢复到正常。肝毒性伴随肝组织结构改变以及硫代巴比妥酸反应性物质(TBARS)、共轭二烯(CD)和羰基蛋白(CP)增加,同时几种评估的抗氧化酶如超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)和过氧化氢酶(CAT)减少。其可药用性、药代动力学性质和分子对接试验支持了[具体物质名称未给出]体内保护作用的研究结果。这些结果证实了[具体物质名称未给出]在该实验性肝硬化模型中的调节抗氧化和肝保护潜力。[具体物质名称未给出]的植物化学物质是进一步药物探索和药物设计的良好候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/490c/9321387/615ec807b457/life-12-01092-g001.jpg

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