Alterations in response to resistin induced oxidative stress in circulating leukocytes from patients with nonalcoholic fatty liver disease (NAFLD)

Abstract

We previously demonstrated that Resistin (RES) decrease reactive oxygen species levels (ROS) in peripheral blood mononuclear cells (PBMC) in non-NAFLD, but not in NAFLD patients. To further evaluate RES effects on oxidative stress and on antioxidant defenses (Aox) in PBMC from NAFLD patients, PBMC were cultured in presence/absence of RES (20 ng/ml) for 24h. PBMC from NAFLD patients had higher baseline ROS levels (1353 ± 498 vs. 468 ± 89, vs. non-NAFLD cells). In addition, PBMC from NAFLD patients showed lower superoxide dismutase (SOD) and glutathione reductase (GRd) activities, and higher glutathione peroxidase activity (p <0.05) than non-NAFLD PBMC. 24h incubation with RES induced an increase in catalase and GRd activities (p<0.01), and a decrease in SOD activity (p< 0.05) and glutathione content (p<0.05) in non-NAFLD PBMC. However, RES could not modulate enzymatic activities in PBMC from NALFD patients. In conclusion, RES presence favored the decrease in ROS in non-NAFLD PBMC by modulating Aox enzymes and GSH redox state, but not in PBMC from NAFLD patients. Redox signaling alterations would favor the inflammatory state and the progression of NALFD. The regulatory mechanisms controlled by Res could be used as potential therapeutic targets in NAFLD patients.