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Toxicology. 2019 Jul 19;425:152248. doi: 10.1016/j.tox.2019.152248. [Epub ahead of print]

Curcumin protects against methylmercury-induced cytotoxicity in primary rat astrocytes by activating the Nrf2/ARE pathway independently of PKCδ.

Author information

1
Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
2
Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China; Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
3
Department of Pharmacology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
4
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, Shanghai 200032, China.
5
Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77550-1106, USA.
6
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
7
Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China; Center for Experimental Research, Kunshan Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu 215132, China. Electronic address: lurz@ujs.edu.cn.

Abstract

Methylmercury (MeHg) is a ubiquitous environmental toxicant that leads to long-lasting neurological deficits in animals and humans. Curcumin, a polyphenol obtained from the rhizome of turmeric, has well-known antioxidant functions. Here, we evaluated curcumin's efficacy in mitigating MeHg-induced cytotoxicity and further investigated the underlying mechanism of this neuroprotection in primary rat astrocytes. Pretreatment with curcumin (2, 5, 10 and 20 μM for 3, 6, 12 or 24 h) protected against MeHg-induced (5 μM for 6 h) cell death in a time and dose-dependent manner. Curcumin (2, 5, 10 or 20 μM) pretreatment for 12 h significantly ameliorated the MeHg-induced astrocyte injury and oxidative stress, as evidenced by morphological alterations, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) generation, and glutathione (GSH) and catalase (CAT) levels. Moreover, curcumin pretreatment increased Nrf2 nuclear translocation and downstream enzyme expression, heme oxygenase-1 (HO-1) and NADPH quinone reductase-1 (NQO1). Knockdown of Nrf2 with siRNA attenuated the protective effect of curcumin against MeHg-induced cell death. However, both the pan-protein kinase C (PKC) inhibitor, Ro 31-8220, and the selective PKCδ inhibitor, rottlerin, failed to suppress the curcumin-activated Nrf2/Antioxidant Response Element(ARE) pathway and attenuate the protection exerted by curcumin. Taken together, these findings confirm that curcumin protects against MeHg-induced neurotoxicity by activating the Nrf2/ARE pathway and this protection is independent of PKCδ activation. More studies are needed to understand the mechanisms of curcumin cytoprotection.

KEYWORDS:

Astrocytes; Curcumin; Methylmercury; Nrf2; PKCδ

PMID:
31330227
DOI:
10.1016/j.tox.2019.152248

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