Ferrostatin‑1 alleviates liver injury via decreasing ferroptosis following ricin toxin poisoning in rat

Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved..

Ricin is a highly toxic plant toxin that can cause multi-organ failure, especially liver dysfunction, and is a potential bioterrorism agent. Despite the serious public health challenge posed by ricin, effective therapeutic for ricin-induced poisoning is currently unavailable. Therefore, it is important to explore the mechanism of ricin poisoning and develop appropriate treatment protocols accordingly. Previous studies have shown that lipid peroxidation and iron accumulation are associated with ricin poisoning. Ferroptosis is an iron-dependent form of cell death caused by excessive accumulation of lipid peroxide. The role and mechanism of ferroptosis in ricin poisoning are unclear and require further study. We investigated the effect of ferroptosis on ricin-induced liver injury and further elucidated the mechanism. The results showed that ferroptosis occurred in the liver of ricin-intoxicated rats, and Ferrostatin‑1 could ameliorate hepatic ferroptosis and thus liver injury. Ricin induced liver injury by decreasing hepatic reduced glutathione and the protein level of glutathione peroxidase 4 and Solute Carrier Family 7 Member 11, increasing iron, malondialdehyde and reactive oxygen species, and mitochondrial damage, whereas Ferrostatin‑1 pretreatment increased hepatic reduced glutathione and the protein level of glutathione peroxidase 4 and Solute Carrier Family 7 Member 11, decreased iron, malondialdehyde, and reactive oxygen species, and ameliorated mitochondrial damage, thereby alleviated liver injury. These results suggested that ferroptosis exacerbated liver injury after ricin poisoning and that inhibition of ferroptosis may be a novel strategy for the treatment of ricin poisoning.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:503

Enthalten in:

Toxicology - 503(2024) vom: 02. März, Seite 153767

Sprache:

Englisch

Beteiligte Personen:

Lin, Ruijiao [VerfasserIn]
Jia, Zijie [VerfasserIn]
Chen, Hongbing [VerfasserIn]
Xiong, Hongli [VerfasserIn]
Bian, Cunhao [VerfasserIn]
He, Xin [VerfasserIn]
Wei, Bi [VerfasserIn]
Fu, Junfeng [VerfasserIn]
Zhao, Minzhu [VerfasserIn]
Li, Jianbo [VerfasserIn]

Links:

Volltext

Themen:

4Y8F71G49Q
9009-86-3
Cyclohexylamines
E1UOL152H7
EC 1.11.1.12
Ferroptosis
Ferrostatin‑1
Ferrostatin-1
GAN16C9B8O
Glutathione
Hepatotoxicity
Iron
Journal Article
Malondialdehyde
Phenylenediamines
Phospholipid Hydroperoxide Glutathione Peroxidase
Reactive Oxygen Species
Ricin
Ricin poisoning

Anmerkungen:

Date Completed 20.03.2024

Date Revised 20.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.tox.2024.153767

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369277724