Oltipraz attenuated cerebral ischemia-reperfusion injury through inhibiting the oxidative stress and ferroptosis in mice.

Autor: Jian W; The First College of Clinical Medical Science, China Three Gorges University, China; Institute of Anesthesia and Critical Care Medicine, China Three Gorges University, China; Yichang Central People's Hospital, Hubei, China., Ma H; The First College of Clinical Medical Science, China Three Gorges University, China; Yichang Central People's Hospital, Hubei, China., Hu Y; The First College of Clinical Medical Science, China Three Gorges University, China; Institute of Anesthesia and Critical Care Medicine, China Three Gorges University, China; Yichang Central People's Hospital, Hubei, China., Zhang Q; The First College of Clinical Medical Science, China Three Gorges University, China; Institute of Anesthesia and Critical Care Medicine, China Three Gorges University, China; Yichang Central People's Hospital, Hubei, China., Xu J; The First College of Clinical Medical Science, China Three Gorges University, China; Institute of Anesthesia and Critical Care Medicine, China Three Gorges University, China; Yichang Central People's Hospital, Hubei, China., Jiang J; The First College of Clinical Medical Science, China Three Gorges University, China; Institute of Anesthesia and Critical Care Medicine, China Three Gorges University, China; Yichang Central People's Hospital, Hubei, China., Zhu G; The First College of Clinical Medical Science, China Three Gorges University, China; Yichang Central People's Hospital, Hubei, China., Gong Y; The First College of Clinical Medical Science, China Three Gorges University, China; Institute of Anesthesia and Critical Care Medicine, China Three Gorges University, China; Yichang Central People's Hospital, Hubei, China. Electronic address: gy-yc@163.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Oct 25; Vol. 140, pp. 112800. Date of Electronic Publication: 2024 Aug 02.
DOI: 10.1016/j.intimp.2024.112800
Abstrakt: Oltipraz (OPZ) is a synthetic dithiolethione and is considered a novel activator of nuclear factor E2-related factor 2 (Nrf2). Increasing evidence indicates that Nrf2 protects against cerebral ischemia/reperfusion (I/R) injury by antagonizing ferroptosis and lipid peroxidation. However, the protective effects of OPZ on cerebral I/R injury remain to be elucidated. We investigated the in vitro and in vivo neuroprotective effects of OPZ. Mice were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) to construct an in vivo model and PC12 cells were exposed to oxygen and glucose deprivation/reoxygenation (OGD/R) to establish an in vitro model. OPZ administration reduced the infarct volume and brain water content, and alleviated the neurological deficit of MCAO/R mice. Moreover, OPZ ameliorated MCAO/R-induced oxidative stress by decreasing the levels of 4-HNE and MDA and increasing the activities of SOD and GSH. We also found that OPZ ameliorated MCAO/R-induced ferroptosis by increasing SLC7A11 and GPX4 protein expression and downregulating ACSL4 protein expression. Similarly, the in vitro results revealed that OGD/R-induced oxidative stress and ferroptosis. Finally, mechanistic analysis revealed that OPZ significantly upregulated the Nrf2 expression and Nrf2 knockout (Nrf2 KO) abolished the OPZ-mediated protective effects. Taken together, these findings demonstrate that OPZ ameliorates cerebral I/R injury by suppressing the oxidative stress and ferroptosis.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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