title: Metallothioneins attenuate paraquat-induced acute lung injury in mice through the mechanisms of anti-oxidation and anti-apoptosis.
abstract: Paraquat (PQ) is a widely used herbicide, and lung is the primary target of PQ poisoning. Metallothionein (MT) is a potent antioxidant and free radical scavenger, and has been shown to play a protective role in lung injury induced by different stressors. This study was undertaken to evaluate the protective potential of MT against PQ-induced acute lung injury using MT-I/II null (MT(-/-)) mice. Wild-type (MT(+/+)) mice and MT(-/-) mice were given one intragastric administration of 50mg/kg PQ for 24h, and it was revealed that MT(-/-) mice were more susceptible to PQ-induced acute lung injury than MT(+/+) mice evidenced by the following findings. As compared with MT(+/+) mice, MT(-/-) mice presented more severe histopathological lesions in the lung, higher pulmonary malondialdehyde content, and more reduced pulmonary antioxidative enzymes activities. PQ also induced more apoptosis in pneumocytes from MT(-/-) mice, and the expressions of apoptosis-related proteins Bax, Bcl-2, cleaved-caspase-3, and the ratio of Bax/Bcl-2 were all more significantly increased in PQ-treated MT(-/-) mice. Our results clearly demonstrate that endogenous MT can attenuate PQ-induced acute lung injury, possibly through the mechanisms of anti-oxidation and anti-apoptosis.
authors.affiliation: Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, PR China; Department of Toxicology, School of Public Health, Jilin University, 1163 Xin Min Street, Chaoyang District, Changchun 130021, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ren
authors.affiliation: Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, PR China.
authors.forename: Yi-Mei
authors.initials: YM
authors.lastname: Wang
authors.affiliation: Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, PR China.
authors.forename: Zeng-Ming
authors.initials: ZM
authors.lastname: Zhao
authors.affiliation: Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, PR China.
authors.forename: Ting-Fen
authors.initials: TF
authors.lastname: Zhang
authors.affiliation: Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Toxicology, School of Public Health, Jilin University, 1163 Xin Min Street, Chaoyang District, Changchun 130021, PR China.
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Ren
authors.affiliation: Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, PR China. Electronic address: pengsq@hotmail.com.
authors.forename: Shuang-Qing
authors.initials: SQ
authors.lastname: Peng
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D008297:Male; D008668:Metallothionein / Q000502:physiology*; D051379:Mice; D010269:Paraquat / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D006540:Herbicides; D008668:Metallothionein; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D010269:Paraquat
keywords: Acute lung injury; Apoptosis; Lipid peroxidation; Metallothionein; Paraquat