Mangiferin alleviates arsenic induced oxidative lung injury via upregulation of the Nrf2-HO1 axis
Mangiferin alleviates arsenic induced oxidative lung injury via upregulation of the Nrf2-HO1 axis
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DOI：
10.1016/j.fct.2019.02.022
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发表时间：
2019-04-01
影响因子：
4.3
通讯作者：
Sil, Parames C.
中科院分区：
文献类型：
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作者：
Mahalanobish, Sushweta;Saha, Sukanya;Sil, Parames C.
砷污染的饮用水消耗是世界各地的一个严重的健康问题。慢性无机砷暴露与呼吸功能障碍有关。它会产生各种有害影响，破坏正常的细胞稳态并引发严重的肺部并发症。这项研究阐明了芒果苷（一种天然氧杂蒽酮）对抗砷引起的肺毒性的作用。慢性暴露于10毫克/千克体重的亚砷酸钠（NaAsO2）3个月会突然增加支气管肺泡灌洗液中LDH的释放，产生活性氧（ROS），损害抗氧化防御并扭曲肺泡结构。它通过上调与线粒体、线粒体外和内质网应激介导的细胞凋亡途径相关的各种促凋亡分子的表达，引起显着的炎症爆发并促进细胞死亡的凋亡模式。炎症级联的激活导致肺泡毛细血管屏障破坏和Na+/K+-ATP酶功能受损，从而导致肺泡液清除活性抑制。芒果苷由于其抗炎活性而抑制了这种炎症并减少了肺组织中的炎症细胞浸润。它通过上调 Nrf2-HO1 轴显着恢复抗氧化平衡并抑制肺细胞凋亡。
Arsenic contaminated drinking water consumption is a serious health issue around the world. Chronic inorganic arsenic exposure has been associated with respiratory dysfunctions. It exerts various detrimental effects, disrupting normal cellular homeostasis and turning on severe pulmonary complications. This study elucidated the role of mangiferin, a natural xanthone, against arsenic induced lung toxicity. Chronic exposure of sodium arsenite (NaAsO2) at 10 mg/kg bw for 3 months abruptly increased the LDH release in broncho-alveolar lavage fluid, generated reactive oxygen species (ROS), impaired the antioxidant defense and distorted the alveoli architecture. It caused significant inflammatory outburst and promoted the apoptotic mode of cell death via upregulating the expressions of various proapoptotic molecules related to mitochondrial, extra-mitochondrial and ER stress mediated apoptotic pathway. Activation of inflammatory cascade led to disruption of alveolar capillary barrier and impaired Na+/K+-ATPase function that led to detaining of alveolar fluid clearance activity. Mangiferin due to its anti-inflammatory activity suppressed this inflammation and reduced inflammatory cell infiltration in lung tissue. It significantly restored the antioxidant balance and inhibited apoptosis in lung via upregulating Nrf2-HO1 axis.