Nicotinamide Mononucleotide Ameliorates Silica-Induced Lung Injury through the Nrf2-Regulated Glutathione Metabolism Pathway in Mice.

Abstract

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.

• Authors: Liqun Wang, Manyu Zhao, Rui Qian, Mengzhu Wang, Qixue Bao, Xuxi Chen, Wen Du, Ling Zhang, Tinghong Ye, Yongmei Xie, Ben Zhang, Lijun Peng, Yuqin Yao
• Journal: Nutrients (Nutrients) Vol. 15 Issue 1 (Dec 28 2022) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 36615800 (Publication Type: Journal Article)

Chemical References

• Nicotinamide Mononucleotide
• Antioxidants
• NF-E2-Related Factor 2
• Silicon Dioxide
• Glutathione

Topics

• Mice
• Animals
• Nicotinamide Mononucleotide
• Antioxidants (pharmacology)
• NF-E2-Related Factor 2 (genetics, metabolism)
• Silicon Dioxide (toxicity)
• Lung Injury (chemically induced, drug therapy, prevention & control)
• Silicosis (drug therapy)
• Glutathione