PPAR-γ Agonist Attenuates Hepatic Ischemia-Reperfusion Injury in a Mouse Model by Regulating Kupffer Cell Polarization.

I. Linares, K. Farrokhi, J. Echeverri, M. Kaths, D. Kollman, M. Hamar, P. Urbanellis, S. Ganesh, O. Adeyi, P. Yip, N. Selzner, M. Selzner.

Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada

Meeting: 2017 American Transplant Congress

Abstract number: D50

Keywords: Apoptosis, Ischemia, Liver, Necrosis

Session Information

Session Name: Poster Session D: Ischemic Injury and Organ Preservation Session III

Session Type: Poster Session

Date: Tuesday, May 2, 2017

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall D1

PPAR-γ agonists have shown protective effect on ischemia-reperfusion injury (IRI) in cerebral and renal tissue. The effects of PPAR-γ on hepatic IRI is unclear. We investigated the effects and mechanisms of protection of PPAR-γ agonists on hepatic IRI.

Methods:

Ischemia of 70% of the liver was induced for 60min. PPAR-γ agonist Rosiglitazone (RGZ-3mg/kg) or vehicle (control) were administrated 24 and 1hr before reperfusion. Aspartate aminotransferase (AST) was measured 1, 6, 12 and 24hrs after reperfusion as a marker of hepatocyte injury. H&E and TUNEL staining was performed to evaluate hepatic necrosis and apoptosis, respectively. Flow-cytometry was used to assess Kupffer cells polarization (M2-CD206+, M1-Nitric Oxide +).

Results:

AST in the RGZ group presented significant reduction after 1hr (RGZ: 3092±279 vs Control: 4469±1559, p=0.042), 6hr (RGZ: 7041±3281 vs Control: 12193±4329, p=0.015), and 12hr (RGZ: 5746±868 vs Control: 8608±3560, p=0.049) of reperfusion. TUNEL staining was significantly reduced in the RGZ vs control group at 1hr (RGZ: 2.46±1.47 vs Control: 6.90±2.42, p=0.001) and 6hrs (RGZ: 28±22 vs Control: 54±20, p=0.027) after reperfusion. H&E staining demonstrated a decreased percentage of necrotic tissue in the treated group 24hr (RGZ: 59±15 vs Control 76±12) after reperfusion. Flow-cytometry revealed that previous to the ischemic insult the percentage of M2 Kupffer cells was increased in the RGZ vs control group (RGZ: 9.6±0.7 vs Control: 4.8% ±0.8, p=0.04). Percentage of M1-Kupffer cells polarization was diminished in the treated group when compared with the control group since 1hr after reperfusion (RGZ: 23±10 vs Control: 45±22, p=0.083), this difference became significant 6hs (RGZ: 3.93±3 vs Control: 31±21, p=0.025) and 24hs (RGZ: 4.15±3 vs Control: 17.10±9, p=0.043) following reperfusion.Conclusion:

PPAR-γ reduces hepatic IRI injury and decreases M1 polarization of Kupffer cells. Kupffer cell polarization is a novel target to reduce hepatic reperfusion injury.

CITATION INFORMATION: Linares I, Farrokhi K, Echeverri J, Kaths M, Kollman D, Hamar M, Urbanellis P, Ganesh S, Adeyi O, Yip P, Selzner N, Selzner M. PPAR-γ Agonist Attenuates Hepatic Ischemia-Reperfusion Injury in a Mouse Model by Regulating Kupffer Cell Polarization. Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Linares I, Farrokhi K, Echeverri J, Kaths M, Kollman D, Hamar M, Urbanellis P, Ganesh S, Adeyi O, Yip P, Selzner N, Selzner M. PPAR-γ Agonist Attenuates Hepatic Ischemia-Reperfusion Injury in a Mouse Model by Regulating Kupffer Cell Polarization. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/ppar-agonist-attenuates-hepatic-ischemia-reperfusion-injury-in-a-mouse-model-by-regulating-kupffer-cell-polarization/. Accessed May 17, 2025.

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