title: Chlorogenic acid, a dietary polyphenol, protects acetaminophen-induced liver injury and its mechanism.
abstract: Chlorogenic acid (CGA) is one of the most abundant dietary polyphenols, possessing well-known antioxidant capacity. The present study is designed to observe the protection provided by CGA against acetaminophen (AP)-induced liver injury in mice in vivo and the underlying mechanisms engaged in this process. Serum transaminases analysis and liver histological evaluation demonstrated the protection of CGA against AP-induced liver injury. CGA treatment decreased the increased number of liver apoptotic cells induced by AP in a dose-dependent manner. CGA also inhibited AP-induced cleaved activation of caspase-3, 7. Moreover, CGA reversed AP-decreased liver reduced glutathione (GSH) levels, glutamate-cysteine ligase (GCL) and glutathione reductase activity. Further results showed that CGA increased mRNA and protein expression of the catalytic subunit of GCL (GCLC), thioredoxin (Trx) 1/2 and thioredoxin reductase (TrxR) 1. Furthermore, CGA abrogated AP-induced phospholyated activation of ERK1/2, c-Jun N-terminal kinase (JNK), p38 kinases and molecular signals upstream. The results of this study demonstrate that CGA counteracts AP-induced liver injury at various levels by preventing apoptosis and oxidative stress damage, and more specifically, both the GSH and Trx antioxidant systems and the mitogen-activated protein kinase (MAPK) signaling cascade appear to be engaged in this protective mechanism.
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines and The Shanghai Key Laboratory for Compound Chinese medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China. Electronic address: lily0913@yahoo.cn.
authors.forename: Lili
authors.initials: L
authors.lastname: Ji
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Sheng
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D002726:Chlorogenic Acid / Q000627:therapeutic use*; D005721:Glutamate-Cysteine Ligase / Q000187:drug effects; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D002726:Chlorogenic Acid; D000082:Acetaminophen; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione
keywords: Acetaminophen; Caspase; Chlorogenic acid; GSH; MAPK; Trx