Glutathione metabolism and antioxidant enzymes in patients affected by nonalcoholic steatohepatitis

Background: Oxidative stress and accumulation of excessive fat in the liver may underlie the pathophysiology of nonalcoholic steatoliepatitis (NASH). Given that glutathione blood metabolism may represent an indicator of tissue oxidative status, we analysed the blood profile of various forms of glutathione in children with NASH, and we evaluated the presence of systemic oxidative stress by calculating the oxidised/reduced glutathione ratio (GSSG/GSH). Furthermore, we analysed the catalytic activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione transferase (GST), and glutathione reductase (GR) in blood of patients. Methods: Blood samples were obtained from 21 children with NASH and 28 controls. Total, reduced, oxidised, and proteinbound glutathione concentrations were determined by reversed-phase liquid chromatography with fluorescence detection. Antioxidant enzymes were spectrophotometrically assayed by using specific substrates. Results: Our findings showed a 1.5-fold increase of GSSG in patients, resulting in a significant rise of the GSSG/GSH ratio. SOD, GPx, and GR activities were not significantly different in NASH respect to controls, whereas GST, which provides the second defence line against oxidative stress, was 17.8% increased. Conclusions: Our data demonstrate an impairment of glutathione metabolism and antioxidant enzyme activities in blood of patients with NASH, supporting a consistent role of free radical cytotoxicity in the pathophysiology of the disease. (c) 2005 Elsevier B.V. All rights reserved.