title: Adiponectin protects against paraquat-induced lung injury by attenuating oxidative/nitrative stress.
abstract: The specific mechanisms underlying paraquat (PQ)-induced lung injury remain unknown, which limits understanding of its cytotoxic potential. Although oxidative stress has been established as an important mechanism underlying PQ toxicity, multiple antioxidants have proven ineffective in attenuating the deleterious effects of PQ. Adiponectin, which shows anti-oxidative and antinitrative effects, may have the potential to reduce PQ-mediated injury. The present study determined the protective action of globular domain adiponectin (gAd) on PQ-induced lung injury, and attempted to elucidate the underlying mechanism or mechanisms of action. BALB/c mice were administered PQ, with and without 12 or 36 h of gAd pre-treatment. The pulmonary oxidative/nitrative status was assessed by measuring pulmonary O2•-, superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and 8-hydroxy-2-dydeoxy guanosine (8-OHdG) production, and blood 3-Nitrotyrosine (3-NT). At a dose of 20 mg/kg, PQ markedly increased O2•-, SOD, MDA, NO and 8-OHdG production 3 h post-administration, but did not significantly increase 3-NT levels until 12 h. gAd inhibited these changes in a dose-dependent manner, via transient activation of MDA, followed by attenuation of MDA formation from 6 h onwards. Histological analysis demonstrated that gAd decreased interstitial edema and inflammatory cell infiltration. These results suggest that gAd protects against PQ-induced lung injury by mitigating oxidative/nitrative stress. Furthermore, gAd may be a potential therapeutic agent for PQ-induced lung injury, and further pharmacological studies are therefore warranted.
authors.affiliation: Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yao
authors.affiliation: Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yarong
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yaowen
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.affiliation: Electrocardiogram Department, No.4 West China Teaching Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.
authors.forename: Wayne Bond
authors.initials: WB
authors.lastname: Lau
authors.affiliation: Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zeng
keywords: globular adiponectin; lung injury; nitrative stress; oxidative stress; paraquat