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对用选定抗疟药治疗的感染伯氏疟原虫小鼠的肝脏抗氧化状态和线粒体膜组成的评估。

Assessment of liver antioxidant status and mitochondrial membrane composition of Plasmodium berghei-infected mice treated with selected antimalarials.

作者信息

Adisa Rahmat Adetutu, Sulaimon Lateef Adegboyega

机构信息

Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-araba, P.M.B. 12003, Lagos, Nigeria.

出版信息

Acta Biochim Pol. 2017;64(3):485-491. doi: 10.18388/abp.2016_1440. Epub 2017 Aug 9.

Abstract

The present study was aimed at determining and comparing the effects of Artecxin (ART), P - Alaxin (P-ALA), Lonart (LON) and Chloroquine (CQ) on oxidative stress parameters and mitochondrial membrane composition in the course of malaria infection. Six groups of five mice each categorized as healthy control (non-parasitized non-treated group), parasitized-non-treated (PnT), parasitized-chloroquine-treated (positive control), parasitized-Artecxin, -Lonart and -P-Alaxin-treated groups were used for the study. Hepatic antioxidant status was assessed with levels of malondialdehyde (MDA) and reduced glutathione (GSH) as well as activity of superoxide dismutase (SOD) and catalase (CAT) in the post mitochondrial and mitochondrial fractions. Mitochondrial membrane integrity was also evaluated with activity of succinate dehydrogenase and levels of phospholipids, cholesterol and proteins in the liver mitochondria. Results revealed that treatment of parasitized mice with the antimalarial drugs significantly (p<0.05) decreased hepatic malondialdehyde (MDA) and mitochondrial membrane phospholipids compared to parasitized untreated group. On the other hand, significantly (p<0.05) elevated succinate dehydrogenase (SDH) activity, mitochondrial membrane cholesterol level, GSH concentration, catalase (CAT) and superoxide dismutase (SOD) activity in the post mitochondrial fraction were obtained. Thus, antimalarial drugs distort mitochondrial membrane integrity and electron transfer but reduce the malaria-induced oxidative stress on the host.

摘要

本研究旨在确定并比较青蒿素(ART)、帕罗西汀(P-ALA)、氯硝柳胺(LON)和氯喹(CQ)在疟疾感染过程中对氧化应激参数和线粒体膜组成的影响。将六组每组五只小鼠分为健康对照组(未感染未治疗组)、感染未治疗组(PnT)、感染氯喹治疗组(阳性对照组)、感染青蒿素治疗组、感染氯硝柳胺治疗组和感染帕罗西汀治疗组进行研究。通过测定线粒体后和线粒体部分中丙二醛(MDA)水平、还原型谷胱甘肽(GSH)水平以及超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性来评估肝脏抗氧化状态。还通过测定肝脏线粒体中琥珀酸脱氢酶活性、磷脂、胆固醇和蛋白质水平来评估线粒体膜完整性。结果显示,与感染未治疗组相比,用抗疟药物治疗感染小鼠可显著(p<0.05)降低肝脏丙二醛(MDA)和线粒体膜磷脂水平。另一方面,线粒体后部分中琥珀酸脱氢酶(SDH)活性、线粒体膜胆固醇水平、GSH浓度、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)活性显著(p<0.05)升高。因此,抗疟药物会破坏线粒体膜完整性和电子传递,但可减轻疟疾对宿主引起的氧化应激。

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