Adiponectin protects against paraquat-induced lung injury by attenuating oxidative/nitrative stress.
Adiponectin protects against paraquat-induced lung injury by attenuating oxidative/nitrative stress.
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DOI：
10.3892/etm.2014.2073
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发表时间：
2015-01
影响因子：
2.7
通讯作者：
Zeng Z
中科院分区：
文献类型：
--
作者：
Yao R;Zhou Y;He Y;Jiang Y;Liu P;Ye L;Zheng Z;Lau WB;Cao Y;Zeng Z
百草枯(PQ)引起肺损伤的具体机制尚不清楚，这限制了人们对其细胞毒性潜力的了解。虽然氧化应激已被确定为PQ毒性的一个重要机制，但多种抗氧化剂已被证明在减轻PQ的有害影响方面无效。脂联素具有抗氧化和抗硝化作用，可能具有减轻PQ介导的损伤的潜力。本研究测定了球状结构域脂联素(Gad)对PQ所致肺损伤的保护作用，并试图阐明其作用机制。BALB/c小鼠给予PQ，分别给予Gad预处理12或36 h和不处理12 h或36 h。测定肺组织O2·−、超氧化物歧化酶、丙二醛、一氧化氮、8-羟基-2-脱氧鸟苷(8-OHdG)和血3-硝基酪氨酸(3-NT)含量，评价肺组织氧化/硝化状态。在20 mg/kg剂量下，PQ可显著增加给药后3h的O2·−、超氧化物歧化酶、丙二醛、NO和8-OHdG的生成，但直到12h才显著增加3-NT的水平，GAD通过短暂激活丙二醛，从6h起抑制丙二醛的生成，并呈剂量依赖关系。组织学分析显示，Gad可减轻间质水肿和炎性细胞浸润。这些结果表明，Gad通过减轻氧化/硝化应激对PQ诱导的肺损伤具有保护作用。此外，Gad可能是一种治疗PQ所致肺损伤的潜在药物，因此有必要进行进一步的药理学研究。
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.
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DOI：
10.1016/j.bbrc.2006.02.186
发表时间：
2006-05-05
影响因子：
3.1
作者：
Jung, TW;Lee, JY;Cha, BS
通讯作者：
Cha, BS
影响因子：
3.6
作者：
Kuloglu, M;Ustundag, B;Cinkilinc, N
通讯作者：
Cinkilinc, N
影响因子：
6.5
作者：
Jo, You Hwan;Kim, Kyuseok;Alam, Hasan B.
通讯作者：
Alam, Hasan B.
影响因子：
82.9
作者：
Maeda, N;Shimomura, I;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
影响因子：
105.7
作者：
BULLIVANT, CM
通讯作者：
BULLIVANT, CM