Tripterygium wilfordii Hook.f. ameliorates paraquat-induced lung injury by reducing oxidative stress and ferroptosis via Nrf2/HO-1 pathway

Paraquat (PQ) poisoning can induce acute lung injury and fibrosis and has an extremely high mortality rate. However, no effective treatments for PQ poisoning have been established. In this study, the potential efficacy of Tripterygium wilfordii Hook.f. (TwHF) in alleviating PQ-induced lung injury an...

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Main Authors: Cong-Ying Song, Meng-Xiao Feng, Li Li, Ping Wang, Xuan Lu, Yuan-Qiang Lu
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651323000799
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author Cong-Ying Song
Meng-Xiao Feng
Li Li
Ping Wang
Xuan Lu
Yuan-Qiang Lu
author_facet Cong-Ying Song
Meng-Xiao Feng
Li Li
Ping Wang
Xuan Lu
Yuan-Qiang Lu
author_sort Cong-Ying Song
collection DOAJ
description Paraquat (PQ) poisoning can induce acute lung injury and fibrosis and has an extremely high mortality rate. However, no effective treatments for PQ poisoning have been established. In this study, the potential efficacy of Tripterygium wilfordii Hook.f. (TwHF) in alleviating PQ-induced lung injury and fibrosis was investigated in a mouse model. Mice were randomly assigned to the control, PQ, PQ + TwHF1 (pretreatment before inducing poisoning), and PQ + TwHF2 (treatment after poisoning) groups. The mice in the PQ + TwHF1 group were pretreated with TwHF for 5 days before receiving one dose of PQ (120 mg/kg) and then received a daily oral gavage of the indicated dosages of TwHF until sacrifice. The mice in the PQ + TwHF2 group were treated with TwHF 2 h after PQ exposure until sacrifice. The pathological analysis and Fapi PET/CT showed that treatment with TwHF attenuated lung injury. And TwHF reduced pulmonary oxidative stress, as indicated by the reduction in, malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) levels, as well as by the increase in superoxide dismutase (SOD) levels. Accordingly, the Perls DAB staining showed increased iron concentrations and western blotting revealed a decreased GPX4 expression after PQ exposure, as well as the mitigation of the overexpression of Nrf2 and HO-1 induced by PQ. In conclusion, our study demonstrated the potential of TwHF as a treatment for PQ-induced lung injury and fibrosis. The protective mechanism of this medicinal herb may involve the regulation of ferroptosis.
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spelling doaj.art-389d8fbcbfd6466ea98fffcd9bda5fcc2023-02-20T04:08:32ZengElsevierEcotoxicology and Environmental Safety0147-65132023-03-01252114575Tripterygium wilfordii Hook.f. ameliorates paraquat-induced lung injury by reducing oxidative stress and ferroptosis via Nrf2/HO-1 pathwayCong-Ying Song0Meng-Xiao Feng1Li Li2Ping Wang3Xuan Lu4Yuan-Qiang Lu5Department of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003 Zhejiang, People’s Republic of China; Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou, 310003 Zhejiang, People’s Republic of ChinaDepartment of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003 Zhejiang, People’s Republic of China; Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou, 310003 Zhejiang, People’s Republic of ChinaDepartment of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003 Zhejiang, People’s Republic of China; Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou, 310003 Zhejiang, People’s Republic of ChinaDepartment of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003 Zhejiang, People’s Republic of China; Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou, 310003 Zhejiang, People’s Republic of ChinaDepartment of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003 Zhejiang, People’s Republic of China; Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou, 310003 Zhejiang, People’s Republic of ChinaDepartment of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003 Zhejiang, People’s Republic of China; Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou, 310003 Zhejiang, People’s Republic of China; Correspondence to: Department of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003 Zhejiang, People’s Republic of China.Paraquat (PQ) poisoning can induce acute lung injury and fibrosis and has an extremely high mortality rate. However, no effective treatments for PQ poisoning have been established. In this study, the potential efficacy of Tripterygium wilfordii Hook.f. (TwHF) in alleviating PQ-induced lung injury and fibrosis was investigated in a mouse model. Mice were randomly assigned to the control, PQ, PQ + TwHF1 (pretreatment before inducing poisoning), and PQ + TwHF2 (treatment after poisoning) groups. The mice in the PQ + TwHF1 group were pretreated with TwHF for 5 days before receiving one dose of PQ (120 mg/kg) and then received a daily oral gavage of the indicated dosages of TwHF until sacrifice. The mice in the PQ + TwHF2 group were treated with TwHF 2 h after PQ exposure until sacrifice. The pathological analysis and Fapi PET/CT showed that treatment with TwHF attenuated lung injury. And TwHF reduced pulmonary oxidative stress, as indicated by the reduction in, malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) levels, as well as by the increase in superoxide dismutase (SOD) levels. Accordingly, the Perls DAB staining showed increased iron concentrations and western blotting revealed a decreased GPX4 expression after PQ exposure, as well as the mitigation of the overexpression of Nrf2 and HO-1 induced by PQ. In conclusion, our study demonstrated the potential of TwHF as a treatment for PQ-induced lung injury and fibrosis. The protective mechanism of this medicinal herb may involve the regulation of ferroptosis.http://www.sciencedirect.com/science/article/pii/S0147651323000799ParaquatLung injuryTripterygium wilfordii Hook.f.FerroptosisOxidative stress
spellingShingle Cong-Ying Song
Meng-Xiao Feng
Li Li
Ping Wang
Xuan Lu
Yuan-Qiang Lu
Tripterygium wilfordii Hook.f. ameliorates paraquat-induced lung injury by reducing oxidative stress and ferroptosis via Nrf2/HO-1 pathway
Ecotoxicology and Environmental Safety
Paraquat
Lung injury
Tripterygium wilfordii Hook.f.
Ferroptosis
Oxidative stress
title Tripterygium wilfordii Hook.f. ameliorates paraquat-induced lung injury by reducing oxidative stress and ferroptosis via Nrf2/HO-1 pathway
title_full Tripterygium wilfordii Hook.f. ameliorates paraquat-induced lung injury by reducing oxidative stress and ferroptosis via Nrf2/HO-1 pathway
title_fullStr Tripterygium wilfordii Hook.f. ameliorates paraquat-induced lung injury by reducing oxidative stress and ferroptosis via Nrf2/HO-1 pathway
title_full_unstemmed Tripterygium wilfordii Hook.f. ameliorates paraquat-induced lung injury by reducing oxidative stress and ferroptosis via Nrf2/HO-1 pathway
title_short Tripterygium wilfordii Hook.f. ameliorates paraquat-induced lung injury by reducing oxidative stress and ferroptosis via Nrf2/HO-1 pathway
title_sort tripterygium wilfordii hook f ameliorates paraquat induced lung injury by reducing oxidative stress and ferroptosis via nrf2 ho 1 pathway
topic Paraquat
Lung injury
Tripterygium wilfordii Hook.f.
Ferroptosis
Oxidative stress
url http://www.sciencedirect.com/science/article/pii/S0147651323000799
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