Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients.
Oxidative stress is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In the present study, hepatic and plasma oxidative stress-related parameters were measured and correlated with clinical and histological findings in 31 NAFLD patients showing increased body mass index. Liver protein carbonyl content was enhanced by 403% in patients with steatosis (n=15) compared with control values (n=12), whereas glutathione content, superoxide dismutase (SOD) activity and the ferric reducing ability of plasma (FRAP) were decreased by 57%, 48% and 21% (P<0.05) respectively. No changes in microsomal p-nitrophenol hydroxylation and the total content of cytochrome P450 (CYP) or CYP2E1 were observed. Patients with steatohepatitis (n=16) exhibited protein carbonyl content comparable with that of controls, whereas glutathione content, SOD and catalase activities were decreased by 27%, 64% and 48% (P<0.05). In addition, FRAP values in patients with steatohepatitis were reduced by 33% and 15% (P<0.05) when compared with controls and patients with steatosis respectively, whereas p-nitrophenol hydroxylation (52%) and CYP2E1 content (142%) were significantly increased (P<0.05) compared with controls. It is concluded that oxidative stress is developed in the liver of NAFLD patients with steatosis and is exacerbated further in patients with steatohepatitis, which is associated with CYP2E1 induction. Substantial protein oxidation is followed by proteolysis of the modified proteins, which may explain the co-existence of a diminished antioxidant capacity and protein oxidation in the liver of patients with steatohepatitis.
Videla
Luis A
LA
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Casilla 70058, Santiago-7, Chile. lvidela@machi.med.uchile.cl
Rodrigo
Ramón
R
Orellana
Myriam
M
Fernandez
Virginia
V
Tapia
Gladys
G
Quiñones
Luis
L
Varela
Nelson
N
Contreras
Jorge
J
Lazarte
Raúl
R
Csendes
Attila
A
Rojas
Jorge
J
Maluenda
Fernando
F
Burdiles
Patricio
P
Diaz
Juan C
JC
Smok
Gladys
G
Thielemann
Lilian
L
Poniachik
Jaime
J
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002374:Catalase / Q000032:analysis / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000032:analysis / Q000378:metabolism
D015415:Biomarkers; D002374:Catalase; D019392:Cytochrome P-450 CYP2E1; D013482:Superoxide Dismutase; D005978:Glutathione