Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata, 700054, India.
Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata, 700054, India.
Food Chem Toxicol. 2019 Apr;126:41-55. doi: 10.1016/j.fct.2019.02.022. Epub 2019 Feb 12.
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 (NaAsO) 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.
饮用砷污染的水是全世界面临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，破坏正常的细胞内稳态，并引发严重的肺部并发症。本研究阐明了天然藤黄烷 mangiferin 对砷诱导的肺毒性的作用。亚砷酸钠（NaAsO）以 10mg/kg bw 的剂量连续暴露 3 个月会突然增加支气管肺泡灌洗液中的 LDH 释放，产生活性氧（ROS），破坏抗氧化防御系统，并使肺泡结构变形。它会引起严重的炎症爆发，并通过上调与线粒体、线粒体外和 ER 应激介导的凋亡途径相关的各种促凋亡分子的表达，促进细胞凋亡。炎症级联的激活导致肺泡毛细血管屏障的破坏和 Na/K-ATPase 功能受损，从而阻碍肺泡液清除活性。由于具有抗炎活性，mangiferin 可抑制这种炎症，并减少肺部的炎症细胞浸润。它通过上调 Nrf2-HO1 轴，显著恢复了肺中的抗氧化平衡并抑制了凋亡。
