title: 24-Week Exposure to Oxidized Tyrosine Induces Hepatic Fibrosis Involving Activation of the MAPK/TGF-β1 Signaling Pathway in Sprague-Dawley Rats Model.
abstract: METHODS
  Oxidized tyrosine (O-Tyr) has been widely detected in many consumer protein products. O-Tyr products such as dityrosine (Dityr) and 3-nitrotyrosine (3-NT) are universal biomarkers of protein oxidation and have been demonstrated to be associated with metabolic disorders in biological system. Evaluation of potential intracorporal effects of dietary O-Tyr is important since the mechanism of biological impacts induced by oral oxidized protein products (OPPs) is still limited although we have proved that some dietary OPPs would induce oxidative injury to liver and kidney.
  
  
  RESULTS
  The present study aimed to investigate the dose-dependent hepatic injury caused by oral O-Tyr in rats. 24-week feeding of O-Tyr enhanced aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, increased total bilirubin (TBiL) content, and led to oxidative damage in rats liver. Besides, O-Tyr distinctly increased the phosphorylation of p38 and ERK2 MAPKs and enhanced fibrosis-related TGF-β1 and Smad2/3 levels. Higher extracellular matrix (ECM) indexes (ICTP, PIIINP) and histological examination (HE and Masson staining) also supported dose-dependent hepatic fibrosis caused by O-Tyr.
  
  
  CONCLUSIONS
  These findings reveal that O-Tyr may induce oxidative damage and hepatic fibrosis via MAPK/TGF-β1 signaling pathway, in which ROS together with malondialdehyde (MDA) and OPPs act as the pivotal mediators.
authors.affiliation: The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Zhuqing Leslie
authors.initials: ZL
authors.lastname: Li
authors.affiliation: The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China; The State Key Laboratory of Food Science and Technology, Food Science and Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Shi
authors.affiliation: The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China; The State Key Laboratory of Food Science and Technology, Food Science and Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Le
authors.affiliation: The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Yinyi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001835:Body Weight; D002374:Catalase / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D020935:MAP Kinase Signaling System; D008297:Male; D013058:Mass Spectrometry; D009929:Organ Size; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D034421:Sus scrofa; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D014443:Tyrosine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase