N-Acetylcysteine Reduced Ischemia and Reperfusion Damage Associated with Steatohepatitis in Mice

Abstract

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.

N-acetylcysteine in the Donor, Recipient, or Both Donor and Recipient in Liver Transplantation: A Systematic Review With Meta-analysis and Trial Sequential Analysis

“…7 For decades, a large number of preclinical studies on LT have shown the powerful therapeutic effect of NAC. 4,[8][9][10][11][12] Additionally, as a dietary supplement, NAC has fewer side effects and a well-known safety profile. 13 Therefore, NAC may be a potentially effective drug to treat IRI in transplanted livers.…”

Preservation of Mitochondrial Health in Liver Ischemia/Reperfusion Injury

“…Targeting mitochondria with antioxidants confers protection against oxidative stress arising from ROS and has hepatoprotective effects against LIRI. For example, N -acetylcysteine (NAC) has been reported to reduce liver injury after I/R injury by decreasing ROS levels, proinflammatory cytokines, and cell death [ 30 , 31 ]. Similarly, targeting mitochondria with coenzyme Q10 protects against LIRI by reducing oxidative stress [ 32 , 33 ].…”