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).

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.

• Authors: Bao-Hong Lee, Wei-Hsuan Hsu, Ya-Wen Hsu, Tzu-Ming Pan
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 62 Pg. 413-9 (Dec 2013) ISSN: 1873-6351 [Electronic] England
• PMID: 24036144 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Actins
• Antioxidants
• Collagen Type I
• Collagen Type I, alpha 1 Chain
• Diketopiperazines
• Hydroxamic Acids
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• alpha-smooth muscle actin, mouse
• dimerumic acid
• N(6)-carboxymethyllysine
• Mok protein, mouse
• Mitogen-Activated Protein Kinases
• Lysine

Topics

• Actins (genetics)
• Animals
• Antioxidants (pharmacology)
• Cells, Cultured
• Collagen Type I (genetics)
• Collagen Type I, alpha 1 Chain
• Diketopiperazines (pharmacology)
• Gene Expression Regulation (drug effects)
• Gene Knockdown Techniques
• Hepatic Stellate Cells (drug effects, metabolism, pathology)
• Hydroxamic Acids (pharmacology)
• Liver Cirrhosis (chemically induced, drug therapy, genetics, metabolism)
• Lysine (adverse effects, analogs & derivatives, toxicity)
• Male
• Mice
• Mice, Inbred C57BL
• Mitogen-Activated Protein Kinases (genetics, metabolism)
• NF-E2-Related Factor 2 (genetics, metabolism)
• Oxidative Stress (drug effects)