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. 2022 Jul:151:113111.
doi: 10.1016/j.biopha.2022.113111. Epub 2022 May 17.

Epigallocatechin-3-gallate inhibits osteopontin expression and prevents experimentally induced hepatic fibrosis

Joseph George  1 , Mutsumi Tsuchishima  2 , Mikihiro Tsutsumi  3
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Free article

Epigallocatechin-3-gallate inhibits osteopontin expression and prevents experimentally induced hepatic fibrosis

Joseph George et al. Biomed Pharmacother. 2022 Jul.
Free article

Abstract

Osteopontin (OPN) is a matricellular cytokine and a stress-induced profibrogenic molecule that promotes activation of stellate cells during the pathogenesis of hepatic fibrosis. We studied the protective effects of epigallocatechin-3-gallate (EGCG) to suppress oxidative stress, inhibit OPN expression, and prevent experimentally induced hepatic fibrosis. Liver injury was induced with intraperitoneal injections of N-nitrosodimethylamine (NDMA) in a dose of 1 mg/100 g body weight on 3 consecutive days of a week for 28 days. A group of rats received 0.2 mg EGCG/100 g body weight orally everyday during the study. The animals were sacrificed on day 28th from the beginning of exposure. Serum levels of AST, ALT, OPN, malondialdehyde, collagen type IV, and hyaluronic acid were measured. Immunohistochemistry and/or real-time PCR were performed for α-SMA, 4-HNE, OPN, collagen type I, and type III. Serial administrations of NDMA produced well developed fibrosis and early cirrhosis in rat liver. Treatment with EGCG significantly reduced serum/plasma levels of AST, ALT, OPN, malondialdehyde, collagen type IV, and hyaluronic acid and prevented deposition of collagen fibers in the hepatic tissue. Protein and/or mRNA levels demonstrated marked decrease in the expression of α-SMA, 4-HNE, OPN, collagen type I, and type III. Treatment with EGCG prevented excessive generation of reactive oxygen species, suppressed oxidative stress, significantly reduced serum and hepatic OPN levels, and markedly attenuated hepatic fibrosis. The results indicated that EGCG could be used as a potent therapeutic agent to prevent hepatic fibrogenesis and related adverse events.

Keywords: 4-hydroxy-2-nonenal; Epigallocatechin-3-gallate; Hepatic fibrosis; N-Nitrosodimethylamine; Osteopontin.

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