title: Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism.
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.
authors.affiliation: MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Jia-qi
authors.initials: JQ
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Shi
authors.forename: Xi-ning
authors.initials: XN
authors.lastname: Xu
authors.forename: Si-chong
authors.initials: SC
authors.lastname: Huang
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.forename: Li-li
authors.initials: LL
authors.lastname: Ji
authors.forename: Zheng-tao
authors.initials: ZT
authors.lastname: Wang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011794:Quercetin / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D012333:RNA, Messenger; D008315:Malondialdehyde; D013879:Thioredoxins; D011794:Quercetin; D002251:Carbon Tetrachloride; D054464:Peroxiredoxins; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D013880:Thioredoxin-Disulfide Reductase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione
keywords: HO-1; Hepatotoxicity; Nuclear factor erythroid 2-related factor 2 (Nrf2); Oxidative stress; Peroxiredoxin (Prx); Trx; TrxR