Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism

J Zhejiang Univ Sci B. 2014 Dec;15(12):1039-47. doi: 10.1631/jzus.B1400104.

Abstract

This study observes the therapeutic detoxification of quercetin, a well-known flavonoid, against carbon tetrachloride (CCl4) induced acute liver injury in vivo and explores its mechanism. Quercetin decreased CCl4-increased serum activities of alanine and aspartate aminotransferases (ALT/AST) when orally taken 30 min after CCl4 intoxication. The results of a histological evaluation further evidenced the ability of quercetin to protect against CCl4-induced liver injury. Quercetin decreased the CCl4-increased malondialdehyde (MDA) and reduced the glutathione (GSH) amounts in the liver. It also reduced the enhanced immunohistochemical staining of the 4-hydroxynonenal (4-HNE) in the liver induced by CCl4. Peroxiredoxin (Prx) 1, 2, 3, 5, 6, thioredoxin reductase 1 and 2 (TrxR1/2), thioredoxin 1 and 2 (Trx1/2), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) all play critical roles in maintaining cellular redox homeostasis. Real-time polymerase chain reaction (PCR) results demonstrated that quercetin reversed the decreased mRNA expression of all those genes induced by CCl4. In conclusion, our results demonstrate that quercetin ameliorates CCl4-induced acute liver injury in vivo via alleviating oxidative stress injuries when orally taken after CCl4 intoxication. This protection may be caused by the elevation of the antioxidant capacity induced by quercetin.

Keywords: HO-1; Hepatotoxicity; Nuclear factor erythroid 2-related factor 2 (Nrf2); Oxidative stress; Peroxiredoxin (Prx); Trx; TrxR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antioxidants / chemistry
  • Aspartate Aminotransferases / blood
  • Carbon Tetrachloride / toxicity*
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Glutathione / metabolism
  • Heme Oxygenase-1 / metabolism
  • Immunohistochemistry
  • Liver / drug effects*
  • Liver / pathology
  • Male
  • Malondialdehyde / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred ICR
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress
  • Peroxiredoxins / metabolism
  • Polymerase Chain Reaction
  • Quercetin / chemistry*
  • RNA, Messenger / metabolism
  • Thioredoxin-Disulfide Reductase / metabolism
  • Thioredoxins / metabolism

Substances

  • Antioxidants
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • RNA, Messenger
  • Malondialdehyde
  • Thioredoxins
  • Quercetin
  • Carbon Tetrachloride
  • Peroxiredoxins
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Thioredoxin-Disulfide Reductase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glutathione