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中链2,3-二巯基丁二酸(DMSA)和单异戊基DMSA对大鼠砷化镓诱导的病理性肝损伤的影响。

Meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA effect on gallium arsenide induced pathological liver injury in rats.

作者信息

Flora S J S, Dubey Rupa, Kannan G M, Chauhan R S, Pant B P, Jaiswal D K

机构信息

Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Raod, 474 002, Gwalior, India.

出版信息

Toxicol Lett. 2002 Jun 7;132(1):9-17. doi: 10.1016/s0378-4274(02)00034-6.

Abstract

The effect of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) on gallium arsenide (GaAs) induced liver damage was studied. The oral feeding rat model was used in this study. The animals were exposed to 10 mg/kg GaAs, orally, once daily, 5 days a week for 24 weeks and treated thereafter with single oral daily dose of either 0.3 mmol/kg DMSA or MiADMSA for two course of 5 days treatment. The animals were sacrificed thereafter. Lipid peroxidation was assessed by measuring liver thiobarbituric acid reactive substance (TBARS). Liver damage was assessed by number of biochemical variables and by light microscopy. The activity of superoxide dismutase (SOD) and delta-aminolevulinic acid dehydratase (ALAD) beside reduced glutathione (GSH) concentration was measured in blood. Exposure to GaAs produced a significant reduction in GSH while, increased the oxidized glutathione (GSSG) concentration. Hepatic glutathione peroxidase (GPx) and catalase activity increased significantly while level of serum transaminase increased moderately. Gallium arsenide exposure also produced marked hepatic histopathological lesions. Overall, treatment with MiADMSA proved to be better than DMSA in the mobilization of arsenic and in the turnover of some of the above mentioned GaAs sensitive biochemical alterations. Histopathological lesions also, responded more favorably to chelation treatment with MiADMSA than DMSA.

摘要

研究了内消旋2,3-二巯基丁二酸(DMSA)和单异戊基DMSA(MiADMSA)对砷化镓(GaAs)诱导的肝损伤的影响。本研究采用经口喂养大鼠模型。动物经口暴露于10mg/kg GaAs,每天1次,每周5天,持续24周,此后用0.3mmol/kg DMSA或MiADMSA单剂量经口每日治疗5天,共两个疗程。此后处死动物。通过测量肝脏硫代巴比妥酸反应物质(TBARS)评估脂质过氧化。通过若干生化指标和光学显微镜评估肝损伤。测定血液中超氧化物歧化酶(SOD)、δ-氨基乙酰丙酸脱水酶(ALAD)的活性以及还原型谷胱甘肽(GSH)的浓度。暴露于GaAs导致GSH显著降低,同时氧化型谷胱甘肽(GSSG)浓度升高。肝脏谷胱甘肽过氧化物酶(GPx)和过氧化氢酶活性显著增加,而血清转氨酶水平适度升高。砷化镓暴露还导致明显的肝脏组织病理学损伤。总体而言,在砷的动员以及上述一些对GaAs敏感的生化改变的周转方面,MiADMSA治疗被证明优于DMSA。组织病理学损伤对MiADMSA螯合治疗的反应也比对DMSA的反应更有利。

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