Levels of the oxidative stress marker γ-glutamyltranspeptidase at different stages of nonalcoholic fatty liver disease.
OBJECTIVE
This study investigated oxidative stress in the liver, by determining hepatic expression and serum levels of γ-glutamyltranspeptidase (GGT) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in different stages of nonalcoholic fatty liver disease (NAFLD), and assessed  whether GGT can differentiate between the various stages of NAFLD.


METHODS
Expression of GGT and 8-OHdG was examined in biopsy specimens by immunohistochemistry, and serum GGT and 8-OHdG levels were measured by enzyme-linked immuno sorbent assays in patients with simple fatty liver (n  = 10), nonalcoholic steatohepatitis (NASH; n = 10) and, as a control, in alcoholic liver disease (ALD; n = 10).


RESULTS
Hepatic tissue expression of GGT and 8-OHdG was seen in ALD, NASH and fatty liver patients. The percentage of hepatocytes positive for 8-OHdG expression and  serum 8-OHdG levels was significantly higher in patients with NASH than simple fatty liver. Serum GGT levels were increased in all cases with ALD, NASH and fatty liver, and correlated significantly with serum levels of 8-OHdG in ALD and NASH, but not in simple fatty liver.


CONCLUSIONS
Levels  of GGT in fatty liver patients may compensate for mild oxidative stress by repressing 8-OHdG levels and preventing progression to NASH; however further oxidative stress leads to increased levels of 8-OHdG and the development of NASH.
Department of Gastroenterology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
M
M
Irie
T
T
Sohda
K
K
Iwata
H
H
Kunimoto
A
A
Fukunaga
S
S
Kuno
K
K
Yotsumoto
K
K
Sakurai
H
H
Iwashita
G
G
Hirano
S I
SI
Ueda
K
K
Yokoyama
D
D
Morihara
S
S
Nishizawa
A
A
Anan
Y
Y
Takeyama
M
M
Sakamoto
S
S
Shakado
S
S
Sakisaka
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D005234:Fatty Liver / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D005723:gamma-Glutamyltransferase / Q000097:blood / Q000378:metabolism*
D015415:Biomarkers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005723:gamma-Glutamyltransferase; D003849:Deoxyguanosine