Ischemia-reperfusion damage is attenuated by GQ-11, a peroxisome proliferator-activated receptor (PPAR)-α/γ agonist, after aorta clamping in rats.

Abstract

INTRODUCTION:

Ischemia-Reperfusion (I/R) damage is one of the major challenges in cardiothoracic surgeries and in a pathological manner, is identified by exacerbated damage signals resulted from blood supply restriction and subsequent flow restoration and re‑oxygenation. I/R damage includes cellular dysfunction and death, impairing tissue and organ function. Inflammation and oxidative stress are known to underlie either ischemia or reperfusion, leaded by HIF, TNF-α, NF-κB, IL-6 and ROS formation. However, the available approaches to prevent I/R damage has been unsuccessful so far. As agonists of peroxisome-proliferation activation receptor (PPAR) are described as transcription factors related to anti-inflammatory factors, we proposed to observe the effects of novel dual agonist, GQ-11, in I/R-related damage.

METHODS:

Male, Wistar rats, 60 days age and 305 g body weight average were treated with vehicle, pioglitazone or GQ-11 (20 mg/kg) for 7 consecutive days and were submitted to aorta clamping for 30 min followed by 3 h of reperfusion. 18F-fluorodeoxyglucose (18F-FDG), an analog of glucose associated with inflammation when accumulated, was observed in liver and bowel by positron emission tomography (PET).

RESULTS:

GQ-11 decreased 18F-FDG uptake in liver and bowel when compared to vehicle and pioglitazone. The treatment also modulated inflammatory markers IL-10, TGF-β, IL-6, IL1-β, TNFα, and CCL-2, besides antioxidant enzymes such as catalase, GPx and SOD.

CONCLUSION:

Inflammation and oxidative stress showed to be important processes to be regulated in I/R in order to prevent exacerbated responses that leads to cell/tissue dysfunction and death. PPAR agonists - including GQ-11 - might be promising agents in a strategy to avoid tissue dysfunction and death after cardiothoracic surgeries.

• Authors: Jacqueline Cavalcante Silva, Margherita Bavestrello, Valerio Gazzola, Giovanni Spinella, Bianca Pane, Elena Grasselli, Ilaria Demori, Laura Canesi, Laura Emionite, Michele Cilli, Ambra Buschiazzo, Gianmario Sambuceti, Ivan Rocha Pitta, Marina Galdino Pitta, Patrizia Perego, Domenico Palombo, Dulcineia Saes Parra Abdalla
• Journal: Life sciences (Life Sci) Vol. 297 Pg. 120468 (May 15 2022) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 35288175 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• PPAR alpha
• PPAR gamma

Topics

• Animals
• Aorta (pathology)
• Constriction
• Male
• PPAR alpha
• PPAR gamma (agonists)
• Rats
• Rats, Wistar
• Reperfusion Injury (drug therapy, pathology, prevention & control)