Oxidative stress on ischemia/reperfusion injury in mice with non-alcoholic hepatic steatosis or steatohepatitis

ABSTRACT

Abstract Purpose: To evaluate the oxidative stress, resulting from ischemia and hepatic reperfusion, in mice with non-alcoholic hepatic steatosis and steatohepatitis. Methods: C57BL/6 male mice were used. Part of them were ob/ob mice, and the other part was fed with standard or MCD diets - this last used to develop steatohepatitis. The animals - MCD-I/R, ob/ob-I/R and I/R groups - were submitted to 30 minutes of partial hepatic ischemia, followed by reperfusion for 24 hours. The blood was collected, for biochemical analysis of AST, and the liver removed for assessment of TBARS and nitrite, and of histology. Results: After the I/R, the animal fed with MCD diet presented higher AST levels (MCD-I/R 967±349U/L / ob/ob-I/R 606±18 U/L / I/R 311±172 U/L), TBARS (MCD-I/R 7±1 nM/mg protein / ob/ob-I/R 3±1 nM/mg protein / I/R 3±1 nM/mg protein) and nitrite (MCD-I/R 614±87 µg/mL / ob/ob-I/R 512±81 µg/mL / I/R 459±29 µg/mL) than the ob/ob mice, when both groups were compared to animals fed with standard diet. Regarding histology, the steatosis level (azonal macrovesicular steatosis of level 3 - >66%) and hepatic fibrosis (periportal and perisinusoidal of level 2) was also more intense, but both animal models presented lobular inflammation of level 3 (>66%). Conclusions: The murine model fed with MCD diet is suitable for the assessment of oxidative stress in hepatic I/R injury associated with the nonalcoholic fatty liver disease. Although both murine models showed inflammatory infiltrate and macro and micro vesicular steatosis.