Melatonin protects bone against cadmium-induced toxicity via activation of Wnt/β-catenin signaling pathway

IF 2.8 4区医学 Q2 TOXICOLOGY

Toxicology Mechanisms and Methods Pub Date : 2019-12-06 DOI:10.1080/15376516.2019.1701595

Latifa Knani, M. Venditti, Safa Kechiche, M. Banni, I. Messaoudi, S. Minucci

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引用次数: 17

Abstract

Abstract Among heavy metals, cadmium (Cd) is one of the most toxic for health due to it accumulation in several tissues including bone. Since melatonin (MLT) favors new bone formation through several pathways including Wnt/β-catenin, here we assessed whether MLT has a protective role against Cd induced toxicity in the rat bone tissue. Adult male Wistar rats receiving 50 mg CdCl2/L and/or 3 mg/L MLT were used and were sacrificed 30 days after the treatment. Femurs and plasma were collected and analyzed by various biochemicals, molecular and histological investigation. The results showed that Cd exposure induced bone disorder characterized by histopathological alterations, a decreased alkaline phosphatase activity and plasmatic concentration of osteocalcin. Moreover, also the expression levels of some osteogenic-related genes (Runx2, Ocn and Alp) were down-regulated after Cd treatment. Since mechanistically Cd toxicity reduced the Kinase activity of GSK3β and protein levels of Wnt3a and β-catenin, we observed that MLT administration significantly ameliorated the toxic effects induced by the metal. Our findings provide clues about a potential protective effect of MLT against Cd-induced bone metabolism destruction and that the protection was partially mediated via the Wnt/β-catenin signaling pathway.

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褪黑素通过激活Wnt/β-catenin信号通路保护骨骼免受镉诱导的毒性

在重金属中，镉(Cd)可在包括骨骼在内的多种组织中积累，是对健康危害最大的重金属之一。由于褪黑激素(MLT)通过包括Wnt/β-catenin在内的几种途径促进新骨形成，因此我们在这里评估了MLT是否对Cd诱导的大鼠骨组织毒性具有保护作用。成年雄性Wistar大鼠接受50 mg CdCl2/L和/或3 mg/L MLT治疗，30天后处死。采集股骨和血浆，进行各种生化、分子和组织学分析。结果表明，Cd暴露引起骨紊乱，表现为组织病理学改变、碱性磷酸酶活性降低和血浆骨钙素浓度降低。此外，一些成骨相关基因(Runx2、Ocn、Alp)的表达水平也在Cd处理后下调。由于Cd毒性机制降低了GSK3β激酶活性和Wnt3a和β-catenin蛋白水平，我们观察到MLT显著改善了金属诱导的毒性作用。我们的研究结果为MLT对cd诱导的骨代谢破坏的潜在保护作用提供了线索，并且这种保护部分是通过Wnt/β-catenin信号通路介导的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology Mechanisms and Methods TOXICOLOGY-

自引率

3.10%

发文量

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.