Animal Models of Steatosis (NAFLD) and Steatohepatitis (NASH) Exhibit Hepatic Lobe-Specific Gelatinases Activity and Oxidative Stress
Articolo
Data di Pubblicazione:
2019
Citazione:
Animal Models of Steatosis (NAFLD) and Steatohepatitis (NASH) Exhibit Hepatic Lobe-Specific Gelatinases Activity and Oxidative Stress / G. Palladini, L.G. Di Pasqua, C. Berardo, V. Siciliano, P. Richelmi, S. Perlini, A. Ferrigno, M. Vairetti. - In: CANADIAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY. - ISSN 2291-2789. - 2019(2019), pp. 5413461.1-5413461.9. [10.1155/2019/5413461]
Abstract:
Animal models of obstructive cholestasis and ischemia/reperfusion damage have revealed the functional heterogeneity of liver lobes. This study evaluates this heterogeneity in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) rat models. Twelve-week-old Obese and Lean male Zucker rats were used for NAFLD. Eight-week-old male Wistar rats fed with 8-week methionine-choline-deficient (MCD) diet and relative control diet were used for NASH. Gelatinase (MMP-2; MMP-9) activity and protein levels, tissue inhibitors of metalloproteinase (TIMPs), reactive oxygen species (ROS), and thiobarbituric acid-reactive substances (TBARS) were evaluated in the left (LL), median (ML), and right liver (RL) lobes. Serum hepatic enzymes and TNF-alpha were assessed. An increase in gelatinase activity in the NASH model occurred in RL compared with ML. TIMP-1 and TIMP-2 displayed the same trend in RL as ML and LL. Control diet RL showed higher MMP-9 activity compared with ML and LL. No significant lobar differences in MMP-2 activity were detected in the NAFLD model. MMP-9 activity was not detectable in Zucker rats. TIMP-1 was lower in LL when compared with ML while no lobar differences were detectable for TIMP-2 in either Obese or Lean Zucker rats. Control diet rats exhibited higher ROS formation in LL versus RL. Significant increases in TBARS levels were observed in LL versus ML and RL in control and MCD rats. The same trend for ROS and TBARS was found in Obese and Lean Zucker rats. An increased serum TNF-alpha occurred in MCD rats. A lobar difference was detected for MMPs, TIMPs, ROS, and TBARS in both MCD and Zucker rats. Higher MMP activation in RL and higher oxidative stress in the LL, compared with the other lobes studied, supports growing evidence for functional heterogeneity among the liver lobes occurring certainly in both NAFLD and NASH rats.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Animals; Disease Models; Animal; Gelatinases; Liver; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Non-alcoholic Fatty Liver Disease; Obesity; Rats; Rats; Wistar; Rats; Zucker; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Oxidative Stress
Elenco autori:
G. Palladini, L.G. Di Pasqua, C. Berardo, V. Siciliano, P. Richelmi, S. Perlini, A. Ferrigno, M. Vairetti
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