Matsagar Shailesh Vilas, Singh Rakesh Kumar
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Raebareli, Lucknow, Uttar Pradesh, India.
J Biochem Mol Toxicol. 2024 Dec;38(12):e70086. doi: 10.1002/jbt.70086.
NRF2 is a nuclear transcription factor involved in the cellular protection against oxidative stress and inflammatory signaling. Sulforaphane is a known NRF2 activator used for its strong antioxidant and anti-inflammatory activity through regulation of Keap-1-HO-1 pathway. However, there is a limited exploration about the role of NRF2 activator, sulforaphane in regulation of poly(I:C)-induced oxidative stress, inflammation and injury in lung. Therefore, we aimed to evaluate the therapeutic effect of sulforaphane in poly(I:C)-induced responses using in vitro as well as in vivo model. We evaluated oxidative stress and inflammatory cytokines in poly(I:C)-induced RAW264.7 cells. We also employed in vivo animal study to evaluate tissue oxidative-antioxidative balance along with expression of NRF2, Keap-1, histopathological assessment by hematoxylin-eosin staining and picrosirius red staining to explore the protective mechanisms of sulforaphane in poly(I:C)-induced mouse model. Our results indicated that sulforaphane increased the expression of NRF2 and its downstream proteins. In addition, sulforaphane alleviated poly(I:C)-induced activation of the oxidative and pro-inflammatory pathways, histopathological changes, depleted expression of GSH and superoxide dismutase in lung tissue. This study suggested that sulforaphane may be one of the useful therapeutic alternatives for poly(I:C) induced lung injury and inflammation.
NRF2是一种核转录因子，参与细胞对氧化应激和炎症信号的保护。萝卜硫素是一种已知的NRF2激活剂，通过调节Keap-1-HO-1途径发挥强大的抗氧化和抗炎活性。然而，关于NRF2激活剂萝卜硫素在调节聚肌苷酸-聚胞苷酸（poly(I:C)）诱导的肺部氧化应激、炎症和损伤中的作用，研究较少。因此，我们旨在使用体外和体内模型评估萝卜硫素对poly(I:C)诱导反应的治疗效果。我们评估了poly(I:C)诱导的RAW264.7细胞中的氧化应激和炎性细胞因子。我们还进行了体内动物研究，以评估组织氧化-抗氧化平衡以及NRF2、Keap-1的表达，通过苏木精-伊红染色和天狼星红染色进行组织病理学评估，以探讨萝卜硫素在poly(I:C)诱导的小鼠模型中的保护机制。我们的结果表明，萝卜硫素增加了NRF2及其下游蛋白的表达。此外，萝卜硫素减轻了poly(I:C)诱导的氧化和促炎途径的激活、组织病理学变化以及肺组织中谷胱甘肽（GSH）和超氧化物歧化酶表达的减少。这项研究表明，萝卜硫素可能是治疗poly(I:C)诱导的肺损伤和炎症的有效治疗选择之一。
