Bixin protects against particle-induced long-term lung injury in an NRF2-dependent manner†,Toxicology Research

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Bixin protects against particle-induced long-term lung injury in an NRF2-dependent manner†
Toxicology Research ( IF 2.2 ) Pub Date : 2018-01-11 00:00:00 , DOI: 10.1039/c7tx00304h
Lian Xue ₁ , Hong Zhang ₁ , Jie Zhang ₁ , Bingyan Li ₂ , Zengli Zhang ₁ , Shasha Tao _{1,

3}

Affiliation

Scope: Particle-induced lung injury is a kind of comprehensive pulmonary disease with not only inflammation but also fibrosis. Bixin is a natural compound that is widely used as a food additive. Our previous studies demonstrated that bixin could alleviate inflammation in ventilation-induced acute lung injury as well as UV-exposure caused skin damage. But whether it could depress silica-induced long-term comprehensive lung injury and the mechanism of bixin in this protection have not yet been studied. Methods: A murine SiO₂-induced long-term comprehensive lung injury model was established through silica intratracheal instillation. To elucidate the effects and mechanisms of bixin in silica-induced pulmonary inflammation and fibrosis, we treated mice with bixin following silica instillation. Results: Bixin treatment attenuated the accumulation of inflammatory cells which significantly ameliorated pathological inflammation and fibrotic development in the lungs. In addition, intraperitoneal (i.p.) injection of bixin in mice led to the upregulation of the NRF2 response in the lungs. Since alveolar macrophage activation plays a vital role in the initiation and progression of this injury, the mechanism was further studied in the THP-1 macrophage cells. Bixin activated NRF2 signals via blocking KEAP1 mediated ubiquitylation and degradation of NRF2. Conclusions: Our work has brought insights into exploring anti-particle-induced lung injury activities in the daily consumption of natural products. In addition, our study also inspires the discovery of new beneficial effects of bixin and its application in the treatment of other inflammatory diseases.

中文翻译：

Bixin 以 NRF2 依赖性方式防止颗粒引起的长期肺损伤†

适用范围：颗粒物引起的肺损伤是一种既有炎症又有纤维化的综合性肺部疾病。红木素是一种天然化合物，广泛用作食品添加剂。我们之前的研究表明，红木素可以减轻通气引起的急性肺损伤以及紫外线照射引起的皮肤损伤中的炎症。但其是否能抑制二氧化硅引起的长期综合性肺损伤以及红木素的保护机制尚未研究。方法：采用二氧化硅气管内滴注法建立小鼠SiO ₂致长期综合性肺损伤模型。为了阐明红木素在二氧化硅诱导的肺部炎症和纤维化中的作用和机制，我们在注射二氧化硅后用红木素治疗小鼠。结果：红木辛治疗减轻了炎症细胞的积累，显着改善了肺部的病理性炎症和纤维化发展。此外，给小鼠腹腔（ip）注射红木素可导致肺部 NRF2 反应上调。由于肺泡巨噬细胞活化在这种损伤的发生和进展中起着至关重要的作用，因此在 THP-1 巨噬细胞中进一步研究了其机制。 Bixin通过阻断 KEAP1 介导的 NRF2 泛素化和降解来激活 NRF2 信号。结论：我们的工作为探索日常食用天然产品中抗颗粒物引起的肺损伤活性提供了见解。此外，我们的研究还启发了红木素新的有益作用的发现及其在治疗其他炎症性疾病中的应用。

更新日期：2018-01-11

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