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

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Silva, Jacqueline Cavalcante ; Bavestrello, Margherita ; Gazzola, Valerio ; Spinella, Giovanni ; Pane, Bianca ; Grasselli, Elena ; Demori, Ilaria ; Canesi, Laura ; Emionite, Laura ; Cilli, Michele ; Buschiazzo, Ambra ; Sambuceti, Gianmario ; Pitta, Ivan Rocha ; Pitta, Marina Galdino ; Perego, Patrizia ; Palombo, Domenico ; Parra Abdalla, Dulcineia Saes

• Document type: Journal article
• Source: Life Sciences; v. 297, p. 11-pg., 2022-05-15.

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 reper-fusion, leaded by HIF, TNF-alpha, NF-kappa B, 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.& nbsp;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. F-18-fluorodeoxyglucose (18F-FDG), an analog of glucose associated with inflammation when accu-mulated, 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-beta, IL-6, IL1-beta, TNF alpha, and CCL-2, besides antioxidant enzymes such as catalase, GPx and SOD.& nbsp;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. (AU)

• FAPESP's process: 12/51316-5 - Study of the activity of biodrugs, PPARs agonists and natural products with therapeutic potential in atherosclerosis
• Grantee: Dulcineia Saes Parra Abdalla
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/16850-1 - Modulation of tissue repair by a new thiazolidine compound (GQ-11) on experimental models of insulin resistance and visceral ischemia
• Grantee: Jacqueline Cavalcante Silva
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 16/00233-3 - "Action of a novel thiazolidinedione (GQ-11) in tissue repair process on experimental models of insulin resistance and vascular surgery.
• Grantee: Jacqueline Cavalcante Silva
• Support Opportunities: Scholarships in Brazil - Doctorate