title: Γ-glutamyl transferase as an early and sensitive marker in ethanol-induced liver injury of rats.
abstract: γ-Glutamyl transferase (GGT) has been regarded as a biological marker of heavy alcohol consumption or hepatobiliary disease such as fatty liver. However, the role of GGT is unknown in the molecular pathway during alcohol-induced liver injury. To determine the role of GGT in alcohol-induced liver injury, Sprague-Dawley rats were administered 22% and 38% ethanol for 3 days as acute and 5 weeks as subchronic model. In serologic analysis, the level of GGT was significantly increased and the level of alanine aminotransferase, aspartate aminotransferase, and total bilirubin were not changed at 3 days and 5 weeks. In histologic analysis, ethanol exposure induced granular deposit formation and sinusoidal dilation in the acute model for 3 days. In the subchronic model for 5 weeks, ethanol exposure further increased the granular deposit formation, sinusoidal congestion, and mild fatty liver change. To determine whether ethanol-exposed liver is associated with changes of antioxidants levels, we performed reverse-transcriptase polymerase chain reaction (RT-PCR) analysis on ethanol-exposed livers of rats. In RT-PCR analysis, the mRNA levels of GPX1 and SOD1 were significantly increased as well as up-regulation of CYP2E1. In the glutathione assay, the level of glutathione was significantly reduced in response to ethanol in rats. Therefore, in this study, ethanol increased the level of serum GGT but depleted the level of glutathione. Moreover, the CYP2E1 was rapidly reflected to ethanol in rats. Taken together, our findings suggest that the elevated GGT is associated with cellular antioxidant defense system, and the CYP2E1 can be used for early diagnosis in alcohol-related diseases.
authors.affiliation: Departments of Thoracic and Cardiovascular Surgery, Kangwon National University Hospital, School of Medicine, Republic of Korea; Stem Cell Institute, Kangwon National University, Republic of Korea.
authors.forename: E
authors.initials: E
authors.lastname: Kim
authors.affiliation: Departments of Thoracic and Cardiovascular Surgery, Kangwon National University Hospital, School of Medicine, Republic of Korea; Stem Cell Institute, Kangwon National University, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Departments of Thoracic and Cardiovascular Surgery, Kangwon National University Hospital, School of Medicine, Republic of Korea; Stem Cell Institute, Kangwon National University, Republic of Korea.
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.affiliation: Departments of Thoracic and Cardiovascular Surgery, Kangwon National University Hospital, School of Medicine, Republic of Korea; Stem Cell Institute, Kangwon National University, Republic of Korea.
authors.forename: J-R
authors.initials: JR
authors.lastname: Park
authors.affiliation: Department of Pulmonary Medicine, Kangwon National University Hospital, School of Medicine, Republic of Korea; Stem Cell Institute, Kangwon National University, Republic of Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Hong
authors.affiliation: College of Veterinary Medicine, Kangwon National University, Republic of Korea; Stem Cell Institute, Kangwon National University, Republic of Korea.
authors.forename: H-M
authors.initials: HM
authors.lastname: Woo
authors.affiliation: Department of Pathology, Kangwon National University Hospital, School of Medicine, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Clinical Diagnosis, Kangwon National University Hospital, School of Medicine, Republic of Korea.
authors.forename: I B
authors.initials: IB
authors.lastname: Seo
authors.affiliation: Departments of Thoracic and Cardiovascular Surgery, Kangwon National University Hospital, School of Medicine, Republic of Korea.
authors.forename: S-M
authors.initials: SM
authors.lastname: Ryu
authors.affiliation: Departments of Thoracic and Cardiovascular Surgery, Kangwon National University Hospital, School of Medicine, Republic of Korea.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Departments of Thoracic and Cardiovascular Surgery, Kangwon National University Hospital, School of Medicine, Republic of Korea; Stem Cell Institute, Kangwon National University, Republic of Korea.
authors.forename: S-M
authors.initials: SM
authors.lastname: Park
authors.affiliation: Departments of Thoracic and Cardiovascular Surgery, Kangwon National University Hospital, School of Medicine, Republic of Korea; Stem Cell Institute, Kangwon National University, Republic of Korea. Electronic address: seran.yang@gmail.com.
authors.forename: S-R
authors.initials: SR
authors.lastname: Yang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D042241:Early Diagnosis; D000431:Ethanol; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000175:diagnosis / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D008297:Male; D018384:Oxidative Stress; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000097:blood*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D000431:Ethanol; D005979:Glutathione Peroxidase; D019392:Cytochrome P-450 CYP2E1; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D001663:Bilirubin; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat