Nicotinamide Mononucleotide Ameliorates Silica-Induced Lung Injury through the Nrf2-Regulated Glutathione Metabolism Pathway in Mice.
Liqun WangManyu ZhaoRui QianMengzhu WangQixue BaoXuxi ChenWen DuLing ZhangTinghong YeYongmei XieBen ZhangLijun PengYuqin YaoPublished in: Nutrients (2022)
Nicotinamide mononucleotide (NMN) is a natural antioxidant approved as a nutritional supplement and food ingredient, but its protective role in silicosis characterized by oxidative damage remains unknown. In this study, we generated a silicosis model by intratracheal instillation of silica, and then performed histopathological, biochemical, and transcriptomic analysis to evaluate the role of NMN in silicosis. We found that NMN mitigated lung damage at 7 and 28 days, manifested as a decreasing coefficient of lung weight and histological changes, and alleviated oxidative damage by reducing levels of reactive oxygen species and increasing glutathione. Meanwhile, NMN treatment also reduced the recruitment of inflammatory cells and inflammatory infiltration in lung tissue. Transcriptomic analysis showed that NMN treatment mainly regulated immune response and glutathione metabolism pathways. Additionally, NMN upregulated the expression of antioxidant genes Gstm1 , Gstm2 , and Mgst1 by promoting the expression and nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf2). Gene interaction analysis showed that Nrf2 interacted with Gstm1 and Mgst1 through Gtsm2 . Promisingly, oxidative damage mediated by these genes occurred mainly in fibroblasts. In summary, NMN alleviates silica-induced oxidative stress and lung injury by regulating the endogenous glutathione metabolism pathways. This study reveals that NMN supplementation might be a promising strategy for mitigating oxidative stress and inflammation in silicosis.
Keyphrases
- oxidative stress
- induced apoptosis
- diabetic rats
- nuclear factor
- ischemia reperfusion injury
- immune response
- dna damage
- poor prognosis
- genome wide
- pulmonary fibrosis
- toll like receptor
- reactive oxygen species
- transcription factor
- body mass index
- physical activity
- binding protein
- heat shock
- magnetic resonance imaging
- adipose tissue
- computed tomography
- type diabetes
- nitric oxide
- dna methylation
- anti inflammatory
- gene expression
- long non coding rna
- metabolic syndrome
- dendritic cells
- cell cycle arrest
- cell death