{"title":"Protective Effects of NRF2 Activator Sulforaphane in Polyinosinic:Polycytidylic Acid-Induced In Vitro and In Vivo Model","authors":"Shailesh Vilas Matsagar, Rakesh Kumar Singh","doi":"10.1002/jbt.70086","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>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.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70086","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.