N-Acetylcysteine reduced ischemia and reperfusion damage associated with steatohepatitis in mice

This research was funded by CAPES—PROAP, 2017, Post graduate Program in Surgical Clinics; PQ10/2012—National Council for Scientific and Technological Development (CNPq) grant number: 308995/2012-0.Universidade de São Paulo. Faculdade de Medicina. Department of Surgery. Laboratory of Surgial Physiopathology. São Paulo, SP, Brazil.Universidade de São Paulo. Faculdade de Medicina. Department of Emergency Medicine. São Paulo, SP, Brazil.Universidade de São Paulo. Faculdade de Medicina. Department of Surgery. Laboratory of Surgial Physiopathology. São Paulo, SP, Brazil.Universidade de São Paulo. Faculdade de Medicina. Department of Surgery. Laboratory of Surgial Physiopathology. São Paulo, SP, Brazil / Universidade de São Paulo. Faculdade de Medicina. Hospital de Clinicas. Instituto Central. Department of Surgery. General and Trauma Surgery Division. São Paulo, SP, Brazil.Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Farmacologia. São Paulo, SP, Brazil.Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Farmacologia. São Paulo, SP, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Microscopia Eletrônica. Ananindeua, PA, Brasil.Universidade de São Paulo. Faculdade de Medicina. Department of Surgery. Laboratory of Surgial Physiopathology. São Paulo, SP, Brazil / Universidade de São Paulo. Faculdade de Medicina. Hospital de Clinicas. Instituto Central. Department of Surgery. General and Trauma Surgery Division. São Paulo, SP, Brazil.Universidade de São Paulo. Faculdade de Medicina. Department of Surgery. Laboratory of Surgial Physiopathology. São Paulo, SP, Brazil / Universidade de São Paulo. Faculdade de Medicina. Hospital de Clinicas. Instituto Central. Department of Surgery. General and Trauma Surgery Division. São Paulo, SP, Brazil.N-acetylcysteine (NAC) is a pharmacological alternative with great potential for reducing the deleterious effects of surgical procedures on patients with steatohepatitis. We evaluated the effect of NAC on hepatic ischemia/reperfusion (I/R) injury in C57BL/6J mice, 8 weeks-old, weighing 25–30 g, with steatohepatitis induced by a methionine- and choline-deficient (MCD) diet. Groups: MCD group (steatohepatitis), MCD-I/R group (steatohepatitis plus 30 min of 70% liver ischemia and 24 h of reperfusion), MCD-I/R+NAC group (same as MCD-I/R group plus 150 mg/kg NAC 15 min before ischemia), and control group (normal AIN-93M diet). Liver enzymes and histopathology; nitrite and TBARS (thiobarbituric acid reactive substances) levels; pro-inflammatory cytokines; antioxidants enzymes; Nrf2 (nuclear factor erythroid-2-related factor 2) expression; and apoptosis were evaluated. In the group treated with NAC, reductions in inflammatory infiltration; AST (aspartate aminotransferase), nitrite, and TBARS levels; GPx (gutathione peroxidase) activity; cytokines synthesis; and number of apoptotic cells were observed while the GR (glutathione reductase) activity was increased. No differences were observed in Nfr2 expression or in SOD (superoxide dismutase), CAT (catalase), and GST (glutathione S-transferase) activities. Thus, it may be concluded that NAC exerts beneficial effects on mice livers with steatohepatitis submitted to I/R by reducing oxidative stress, inflammatory response, and cell death