Inhibition of liver fibrosis by solubilized coenzyme Q10: Role of Nrf2 activation in inhibiting transforming growth factor-β1 expression

Hoo Kyun Choi, Yuba Raj Pokharel, Sung Chul Lim, Hyo Kyung Han, Chang Seon Ryu, Sang Kyum Kim, Mi Kyong Kwak, Keon Wook Kang

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Coenzyme Q10 (CoQ10), an endogenous antioxidant, is important in oxidative phosphorylation in mitochondria. It has anti-diabetic and anti-cardiovascular disease effects, but its ability to protect against liver fibrosis has not been studied. Here, we assessed the ability of solubilized CoQ10 to improve dimethylnitrosamine (DMN)-induced liver fibrogenesis in mice. DMN treatments for 3 weeks produced a marked liver fibrosis as assessed by histopathological examination and tissue 4-hydroxyproline content. Solubilized CoQ10 (10 and 30 mg/kg) significantly inhibited both the increases in fibrosis score and 4-hydroxyproline content induced by DMN. Reverse transcription-polymerase chain reaction and Western blot analyses revealed that solubilized CoQ10 inhibited increases in the transforming growth factor-β1 (TGF-β1) mRNA and α-smooth muscle actin (α-SMA) protein by DMN. Interestingly, hepatic glutamate-cysteine ligase (GCL) and glutathione S-transferase A2 (GSTA2) were up-regulated in mice treated with CoQ10. Solubilized CoQ10 also up-regulated antioxidant enzymes such as catalytic subunits of GCL and GSTA2 via activating NF-E2 related factor2 (Nrf2)/antioxidant response element (ARE) in H4IIE hepatoma cells. Moreover, CoQ10's inhibition of α-SMA and TGF-β1 expressions disappeared in Nrf2-null MEF cells. In contrast, Nrf2 overexpression significantly decreased the basal expression levels of α-SMA and TGF-β1 in Nrf2-null MEF cells. These results demonstrated that solubilized CoQ10 inhibited DMN-induced liver fibrosis through suppression of TGF-β1 expression via Nrf2/ARE activation.

Original languageEnglish
Pages (from-to)377-384
Number of pages8
JournalToxicology and Applied Pharmacology
Volume240
Issue number3
DOIs
StatePublished - 1 Nov 2009

Keywords

  • Fibrosis
  • Nrf2
  • Solubilized CoQ10
  • Stellate cell
  • TGF-β1

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