title: Epigallocatechin gallate potentially abrogates fluoride induced lung oxidative stress, inflammation via Nrf2/Keap1 signaling pathway in rats: An in-vivo and in-silico study.
abstract: BACKGROUND
  Since this Nrf2-dependent cellular defense response is able to protect multi-organs, including cancer, neurodegenerative diseases, cardiovascular diseases, inflammation and chronic lung injury. The antioxidant and anti-inflammatory potential of Epigallocatechin gallate (EGCG) and Nrf2/Keap1 signaling mechanisms in pulmonary toxicity have not been clarified. In the present study, we demonstrated that protective efficacy of EGCG against fluoride (Fl) induced oxidative stress mediated lung injury in rats.
  
  
  METHODS
  The animals were divided in to four groups. Group 1: Control rats received normal saline; Group 2 rats received EGCG (40mg/kg/bw) alone for four weeks; Group 3 rats received Fl (25mg/kg/bw) alone for four weeks, Group 4 rats received EGCG (90min before administration) along with Fl for four weeks.
  
  
  RESULTS
  Oral administration of Fl (25mg/kg/bw) significantly (p<0.05) increased the ROS, inflammatory cytokines, lung edema, melonaldehyde (MDA) and myeloperoxidase (MPO) in rats. In addition, upon administration of Fl significantly (p<0.05) decreased the antioxidant status, Nrf2, and HO-1 with increased Keap1 protein. Histological and immunohistochemical (iNOS) study also revealed the Fl induced significant (p<0.05) changes in the lung tissue of rats. Pre-administration of EGCG significantly (p<0.05) improved the antioxidant status, and inhibited the oxidative stress, inflammatory cytokines, and Keap1 protein via the activation of Nrf2 translocation in to the nucleus. Moreover, the molecular docking studies also support the antioxidant potential of EGCG and Nrf2 activation.
  
  
  CONCLUSIONS
  Taken together, our data indicate that EGCG potentially abrogates Fl induced oxidative lung injury by activation of the Nrf2/Keap1 pathway in rats.
authors.affiliation: Department of Zoology, Annamalai University, Annamalainagar 608002, Tamilnadu, India. Electronic address: s.thangapandiyanphd@gmail.com.
authors.forename: Thangapandiyan
authors.initials: T
authors.lastname: Shanmugam
authors.affiliation: Department of Zoology, Annamalai University, Annamalainagar 608002, Tamilnadu, India.
authors.forename: Miltonprabu
authors.initials: M
authors.lastname: Selvaraj
authors.affiliation: Divisions of Bioinformatics, Annamalai University, Annamalainagar 608002, Tamilnadu, India.
authors.forename: Senthilraja
authors.initials: S
authors.lastname: Poomalai
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D005459:Fluorides; D018836:Inflammation Mediators / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D002392:Catechin; C045651:epigallocatechin gallate; D005459:Fluorides
keywords: EGCG; Lung; NaF; Nrf2; ROS; Rat