Suppression of dimerumic acid on hepatic fibrosis caused from carboxymethyl-lysine (CML) by attenuating oxidative stress depends on Nrf2 activation in hepatic stellate cells (HSCs)
Journal
Food and Chemical Toxicology
Journal Volume
62
Pages
413-419
Date Issued
2013
Author(s)
Abstract
Hyperglycemia facilitates the formation of advanced glycation end-products (AGEs) in type-2 diabetes. Evidence indicates that carboxymethyl-lysine (CML) is highly prevalent in diabetes, resulting in hepatic fibrosis. The current study was designed to evaluate the effects of dimerumic acid (DMA) identified from Monascus-fermented products on receptor for AGEs (RAGE) signal and hepatic stellate cells (HSCs) activation by CML treatment. We found that DMA (50. μM) eliminated collagen generation, mRNA expressions of α-smooth muscle actin (α-SMA), platelet-derived growth factor-β receptor (PDGF-βR), and procollagen 1a1 (proCol-1a1) in CML (100. μg/ml)-treated HSCs, and these effects were similar to allyl isothiocyanate (AITC; 50. μM). In addition, the suppression of α-SMA, PDGF-βR, proCol-1a1 by DMA were abolished while nuclear factor-erythroid 2-related factor 2 (Nrf2) silence in CML-treated HSCs. These findings suggested that DMA and AITC increased Nrf2 and glutamate-cysteine ligase (GCL) activities thereby inhibiting oxidative stress caused by CML and showing anti-fibrogentic effect in HSCs. ? 2013 Elsevier Ltd.
Subjects
Advanced glycation end-products (AGEs); Carboxymethyl-lysine (CML); Dimerumic acid (DMA); Hepatic fibrosis; Nuclear factor-erythroid 2-related factor 2 (Nrf2)
SDGs
Other Subjects
6 n carboxymethyllysine; advanced glycation end product receptor; allyl isothiocyanate; alpha smooth muscle actin; collagen; dimerumic acid; glutamate cysteine ligase; messenger RNA; natural product; platelet derived growth factor beta receptor; procollagen; procollagen 1a1; transcription factor Nrf2; unclassified drug; animal cell; animal experiment; animal model; article; cell activation; collagen synthesis; concentration response; controlled study; fermentation; gene expression; liver fibrosis; male; Monascus; mouse; nonhuman; oxidative stress; signal transduction; stellate cell; transcription initiation; Monascus; Advanced glycation end-products (AGEs); Carboxymethyl-lysine (CML); Dimerumic acid (DMA); Hepatic fibrosis; Nuclear factor-erythroid 2-related factor 2 (Nrf2); Actins; Animals; Antioxidants; Cells, Cultured; Collagen Type I; Diketopiperazines; Gene Expression Regulation; Gene Knockdown Techniques; Hepatic Stellate Cells; Hydroxamic Acids; Liver Cirrhosis; Lysine; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; NF-E2-Related Factor 2; Oxidative Stress
Type
journal article