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开环异落叶松脂素二葡萄糖苷可保护大鼠免受镉诱导的氧化应激介导的肾毒性。

Secoisolariciresinol diglucoside protects against cadmium-induced oxidative stress-mediated renal toxicity in rats.

作者信息

Aqeel Tareq, Gurumallu Sunil Chikkalakshmipura, Bhaskar Ashwini, Hashimi Saeed Mujahid, Javaraiah Rajesh

机构信息

Department of Biochemistry, Yuvaraja's College, University of Mysore, Mysuru, 570005, Karnataka, India.

Department of Basic Sciences, Deanship of Preparatory Year and Supporting Studies, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam, 34212, Saudi Arabia.

出版信息

J Trace Elem Med Biol. 2020 Sep;61:126552. doi: 10.1016/j.jtemb.2020.126552. Epub 2020 May 18.

Abstract

BACKGROUND

Cadmium is a well known environmental pollutant and strong toxic heavy metal, that causes oxidative damage to various organs of the body, including the kidney. Cadmium (II) chloride (CdCl) is a water-soluble crystalline form, which exhibits a higher affinity with chlorides at the target site. The current study examined the protective effects of Secoisolariciresinol diglucoside (SDG), a principal lignan extracted from flaxseeds against CdCl-induced renal toxicity in rats.

METHODS

Twenty four healthy male Wistar rats with four groups of six animals each were used in the study. Group-1- Control was administered with saline. Group-2 -was treated with SDG; Group-3 with CdCl alone, and Group-4 were treated with CdCl plus SDG. The effect of Cd on kidney was assessed in terms of various parameters like lipid peroxidation, production of Nitric oxide (NO) and Myeloperoxidase (MPO), and kidney function markers like uric acid, urea, and creatinine. The levels of antioxidant molecules like glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were also measured, apart from histopathological studies.

RESULTS

The animals that received CdCl, exhibited changes in the concentration of Cd in the kidney. The levels of kidney function markers like uric acid, urea, and creatinine were found to be abnormal in serum, and also there was a drastic decrease in the levels of glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. The treatment of SDG significantly decreased (p < 0.05) the levels of NO and MPO in the animals treated with CdCl plus SDG when compared to the animal group treated with CdCl alone. The treatment of SDG before CdCl2 injection exhibited significant changes in the activity of the antioxidant enzymes, which was evidenced by the restoration in their activities, when compared to CdCl2 alone treated group (p < 0.05), as observed in the results of histopathology.

CONCLUSIONS

The findings of the present investigation suggested that SDG exhibited anti-oxidant, anti-apoptotic and renoprotective properties. Thus, SDG may act as a supramolecular binding component and naturally occurring metal chelating agent for metal cations like Cd. Therefore, flaxseed lignan-SDG can be used as a therapeutic agent against nephrotoxicity caused by cadmium. However, detailed future studies are needed to know the underlying mechanism of action of SDG against the Cd and other heavy metals induced nephrotoxicity.

摘要

背景

镉是一种众所周知的环境污染物和强毒性重金属,会对包括肾脏在内的身体各个器官造成氧化损伤。氯化镉(II)(CdCl)是一种水溶性晶体形式,在靶部位与氯化物具有更高的亲和力。本研究检测了从亚麻籽中提取的主要木脂素开环异落叶松脂素二葡萄糖苷(SDG)对氯化镉诱导的大鼠肾毒性的保护作用。

方法

本研究使用了24只健康雄性Wistar大鼠,分为四组,每组6只动物。第1组为对照组,给予生理盐水。第2组用SDG治疗;第3组仅用CdCl治疗,第4组用CdCl加SDG治疗。通过脂质过氧化、一氧化氮(NO)和髓过氧化物酶(MPO)的产生以及尿酸、尿素和肌酐等肾功能指标来评估镉对肾脏的影响。除了组织病理学研究外,还测量了谷胱甘肽含量等抗氧化分子水平以及超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶的活性。

结果

接受CdCl的动物肾脏中镉浓度发生变化。血清中尿酸、尿素和肌酐等肾功能指标水平异常,谷胱甘肽含量以及超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶的活性也大幅下降。与仅用CdCl治疗的动物组相比,用SDG治疗显著降低了(p < 0.05)用CdCl加SDG治疗的动物中NO和MPO的水平。在注射CdCl2之前用SDG治疗,抗氧化酶活性出现显著变化,组织病理学结果显示,与仅用CdCl2治疗的组相比,其活性恢复,证明了这一点(p < 0.05)。

结论

本研究结果表明,SDG具有抗氧化、抗凋亡和肾脏保护特性。因此,SDG可能作为一种超分子结合成分和天然存在的金属阳离子(如Cd)螯合剂。因此,亚麻籽木脂素 - SDG可作为治疗镉引起的肾毒性的药物。然而,需要进一步详细研究以了解SDG对抗Cd和其他重金属诱导的肾毒性的潜在作用机制。

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