title: Epigallocatechin-3-gallate exhibits anti-fibrotic effect by attenuating bleomycin-induced glycoconjugates, lysosomal hydrolases and ultrastructural changes in rat model pulmonary fibrosis.
abstract: Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix components in the alveolar space, which hampers normal respiration process. Pathophysiological enzymes, glycoprotein moieties and matrix degrading lysosomal hydrolases are key markers and play a crucial role in the progression of fibrosis. Bleomycin is an anti-neoplastic drug, used for the treatment of various types of cancers and induces pulmonary fibrosis due its deleterious side effect. Tea catechin epigallocatechin-3-gallate (EGCG) is known for its wide array of beneficial effects. The present study was intended to evaluate the beneficial efficacy of EGCG against bleomycin-induced glycoconjugates, lysosomal hydrolases and ultrastructural changes in the lungs of Wistar rats. Intratracheal instillation of bleomycin (6.5 U/kg body weight) to rats increased the activities of pathophysiological enzymes such as aspartate transaminase, alanine transaminase, lactate dehydrogenase and alkaline phosphatase, which were attenuated upon EGCG treatment. The increased level of hydroxyproline and histopathological parameters in bleomycin-induced rats were decreased upon EGCG treatment. Bleomycin-induced increase in the level of glycoconjugates was restored closer to normal levels on EGCG treatment. Furthermore, the increased activities of matrix degrading lysosomal enzymes in bleomycin-induced rats were reduced upon EGCG supplementation. Treatment with EGCG also attenuated bleomycin-induced ultrastructural changes as observed from transmission electron microscopy studies. The results of the present study put-forward EGCG as a potential anti-fibrotic agent due to its attenuating effect on potential fibrotic markers.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Sriram
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Kalayarasan
authors.forename: Ganapasam
authors.initials: G
authors.lastname: Sudhandiran
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology*; D001761:Bleomycin / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008297:Male; D011658:Pulmonary Fibrosis / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D001761:Bleomycin; D002392:Catechin; C045651:epigallocatechin gallate; D007770:L-Lactate Dehydrogenase