TY - JOUR
T1 - Where ferroptosis inhibitors and paraquat detoxification mechanisms intersect, exploring possible treatment strategies
AU - Rashidipour, Niloofar
AU - Karami-Mohajeri, Somayyeh
AU - Mandegary, Ali
AU - Mohammadinejad, Reza
AU - Wong, Anselm
AU - Mohit, Melika
AU - Salehi, Jafar
AU - Ashrafizadeh, Milad
AU - Najafi, Amir
AU - Abiri, Ardavan
PY - 2020/3/30
Y1 - 2020/3/30
N2 - 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.
AB - 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.
KW - Ferroptosis
KW - Herbicide
KW - Paraquat
KW - Poisoning
KW - PQ
KW - ROS
UR - http://www.scopus.com/inward/record.url?scp=85079666011&partnerID=8YFLogxK
U2 - 10.1016/j.tox.2020.152407
DO - 10.1016/j.tox.2020.152407
M3 - Review Article
C2 - 32061663
AN - SCOPUS:85079666011
SN - 0300-483X
VL - 433-434
JO - Toxicology
JF - Toxicology
M1 - 152407
ER -