Thangapandiyan Shanmugam1, Miltonprabu Selvaraj2, Senthilraja Poomalai3. 1. Department of Zoology, Annamalai University, Annamalainagar 608002, Tamilnadu, India. Electronic address: s.thangapandiyanphd@gmail.com. 2. Department of Zoology, Annamalai University, Annamalainagar 608002, Tamilnadu, India. 3. Divisions of Bioinformatics, Annamalai University, Annamalainagar 608002, Tamilnadu, India.
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. CONCLUSION: Taken together, our data indicate that EGCG potentially abrogates Fl induced oxidative lung injury by activation of the Nrf2/Keap1 pathway in rats.
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. CONCLUSION: Taken together, our data indicate that EGCG potentially abrogates Fl induced oxidative lung injury by activation of the Nrf2/Keap1 pathway in rats.
Authors: Saleh A Almatroodi; Ahmad Almatroudi; Mohammed A Alsahli; Mohammad A Aljasir; Mansoor Ali Syed; Arshad Husain Rahmani Journal: Molecules Date: 2020-06-20 Impact factor: 4.411