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Life Sci. 2019 Aug 15;231:116585. doi: 10.1016/j.lfs.2019.116585. Epub 2019 Jun 18.

NLRP inflammasome as a key role player in the pathogenesis of environmental toxicants.

Author information

1
Department of Immunology, School of Medicine, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
3
Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran, Islamic Republic of Iran.
4
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
5
Department of Pharmacology and Toxicology, School of Medicine, Babol University of Medical Sciences, Babol, Iran. Electronic address: Mohammadhossein.asghari@gmail.com.
6
Department of Pharmacology and Toxicology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.
7
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran. Electronic address: Mohammad@TUMS.Ac.Ir.

Abstract

Exposure to environmental toxicants (ET) results in specific organ damage and auto-immune diseases, mostly mediated by inflammatory responses. The NLRP3 inflammasome has been found to be the major initiator of the associated pathologic inflammation. It has been found that ETs can trigger all the signals required for an NLRP3-mediated response. The exaggerated activation of the NLRP3 inflammasome and its end product IL-1β, is responsible for the pathogenesis caused by many ETs including pesticides, organic pollutants, heavy metals, and crystalline compounds. Therefore, an extensive study of these chemicals and their mechanisms of inflammasome (INF) activation may provide the scientific evidence for possible targeting of this pathway by proposing possible protective agents that have been previously shown to affect INF compartments and its activation. Melatonin and polyunsaturated fatty acids (PUFA) are among the safest and the most studied of these agents, which affect a wide variety of cellular and physiological processes. These molecules have been shown to suppress the NLRP3 inflammasome mostly through the regulation of cellular redox status and the nuclear factor-κB (NF-κB) pathway, rendering them potential promising compounds to overcome ET-mediated organ damage. In the present review, we have made an effort to extensively review the ETs that exert their pathogenesis via the stimulation of inflammation, their precise mechanisms of action and the possible protective agents that could be potentially used to protect against such toxicants.

KEYWORDS:

Crystalline toxicants; Heavy metals; Melatonin; NF-κB; PUFA; Pesticides

PMID:
31226415
DOI:
10.1016/j.lfs.2019.116585
[Indexed for MEDLINE]

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