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Title: | Where ferroptosis inhibitors and paraquat detoxification mechanisms intersect, exploring possible treatment strategies. | Authors: | Najafi A.;Wong A. ;Mohit M.;Salehi J.;Ashrafizadeh M.;Abiri A.;Rashidipour N.;Karami-Mohajeri S.;Mandegary A.;Mohammadinejad R. | Monash Health Department(s): | Monash University - School of Clinical Sciences at Monash Health | Institution: | (Rashidipour) Department of Anesthesiology, Faculty of Allied Medical Sciences, Kerman University of Medical Sciences, Kerman, Iran, Islamic Republic of (Rashidipour, Mohammadinejad, Najafi) Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran, Islamic Republic of (Karami-Mohajeri, Mandegary, Najafi) Department of Toxicology and Pharmacology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran, Islamic Republic of (Mandegary) Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran, Islamic Republic of (Wong) Victorian Poisons Information Centre, Emergency Department and Austin Toxicology Unit, Austin Health, Victoria, Australia (Wong) Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Victoria, Australia (Wong) Centre for Integrated Critical Care, Department of Medicine and Radiology, Melbourne Medical School, University of Melbourne, Victoria, Australia (Mohit) Department of Laboratory Sciences, Sirjan Faculty of Medical Sciences, Kerman University of Medical Sciences, Kerman, Iran, Islamic Republic of (Salehi) Department of Anesthesiology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran, Islamic Republic of (Ashrafizadeh) Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran, Islamic Republic of (Abiri) Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran, Islamic Republic of | Issue Date: | 11-Apr-2020 | Copyright year: | 2020 | Publisher: | Elsevier Ireland Ltd | Place of publication: | Ireland | Publication information: | Toxicology. 433-434 (no pagination), 2020. Article Number: 152407. Date of Publication: 30 March 2020. | Journal: | Toxicology | Abstract: | Paraquat (PQ) is a fast-acting and effective herbicide that is used throughout the world to eliminate weeds. Over the past years, PQ was considered one of the most popular poisoning substances for suicide, and PQ poisoning accounts for about one-third of suicides around the world. Poisoning with PQ may cause multiorgan failure, pulmonary fibrosis, and ultimately death. Exposure to PQ results in the accumulation of PQ in the lungs, causing severe damage and, eventually, fibrosis. Until now, no effective antidote has been found to treat poisoning with PQ. In general, the toxicity of PQ is due to the formation of high energy oxygen free radicals and the peroxidation of unsaturated lipids in the cell. Ferroptosis is the result of the loss of glutathione peroxidase 4 (GPX4) activity that transforms iron-dependent lipid hydroperoxides to lipid alcohols, which are inert in the biological environment. Impaired iron metabolism and lipid peroxidation are increasingly known as the driving agents of ferroptosis. The contribution of ferroptosis to the development of cell death during poisoning with PQ has not yet been addressed. There is growing evidence about the relationship between PQ poisoning and ferroptosis. This raises the possibility of using ferroptosis inhibitors for the treatment of PQ poisoning. In this hypothesis-driven review article, we elaborated how ferroptosis inhibitors might circumvent the toxicity induced by PQ and may be potentially useful for the treatment of PQ toxicity.Copyright © 2020 Elsevier B.V. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1016/j.tox.2020.152407 | PubMed URL: | 32061663 [http://www.ncbi.nlm.nih.gov/pubmed/?term=32061663] | ISSN: | 0300-483X | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/29343 | Type: | Review | Subjects: | iron metabolism lipid peroxidation lung fibrosis multiple organ failure paraquat poisoning pathophysiology SH-SY5Y cell line alpha tocopherol chondroitin sulfate iron deferoxamine dizocilpine ebselen hydroxymethylglutaryl coenzyme A reductase inhibitor lipid hydroperoxide mercaptoethanol norphenazone oxygen radical paraquat phospholipid hydroperoxide glutathione peroxidase propofol unsaturated fatty acid apoptosis detoxification ferroptosis |
Type of Clinical Study or Trial: | Review article (e.g. literature review, narrative review) |
Appears in Collections: | Articles |
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