Animal Models of Steatosis (NAFLD) and Steatohepatitis (NASH) Exhibit Hepatic Lobe-Specific Gelatinases Activity and Oxidative Stress

Giuseppina Palladini, Laura G. Di Pasqua, Clarissa Berardo, Veronica Siciliano, Plinio Richelmi, Stefano Perlini, Andrea Ferrigno, Mariapia Vairetti

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number5413461
JournalCanadian Journal of Gastroenterology and Hepatology
Volume2019
DOIs
Publication statusPublished - Jan 1 2019

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Gelatinases
Fatty Liver
Oxidative Stress
Animal Models
Zucker Rats
Matrix Metalloproteinases
Liver
Thiobarbituric Acid Reactive Substances
Choline
Methionine
Reactive Oxygen Species
Diet
Tissue Inhibitor of Metalloproteinases
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Tumor Necrosis Factor-alpha
Non-alcoholic Fatty Liver Disease
Matrix Metalloproteinase Inhibitors
Cholestasis
Reperfusion Injury

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Animal Models of Steatosis (NAFLD) and Steatohepatitis (NASH) Exhibit Hepatic Lobe-Specific Gelatinases Activity and Oxidative Stress. / Palladini, Giuseppina; Di Pasqua, Laura G.; Berardo, Clarissa; Siciliano, Veronica; Richelmi, Plinio; Perlini, Stefano; Ferrigno, Andrea; Vairetti, Mariapia.

In: Canadian Journal of Gastroenterology and Hepatology, Vol. 2019, 5413461, 01.01.2019.

Research output: Contribution to journalArticle

Palladini, Giuseppina ; Di Pasqua, Laura G. ; Berardo, Clarissa ; Siciliano, Veronica ; Richelmi, Plinio ; Perlini, Stefano ; Ferrigno, Andrea ; Vairetti, Mariapia. / Animal Models of Steatosis (NAFLD) and Steatohepatitis (NASH) Exhibit Hepatic Lobe-Specific Gelatinases Activity and Oxidative Stress. In: Canadian Journal of Gastroenterology and Hepatology. 2019 ; Vol. 2019.
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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.",
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AU - Berardo, Clarissa

AU - Siciliano, Veronica

AU - Richelmi, Plinio

AU - Perlini, Stefano

AU - Ferrigno, Andrea

AU - Vairetti, Mariapia

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