Protective Effects of Pioglitazone in Renal Ischemia–Reperfusion Injury (Riri): Focus on Oxidative Stress and Inflammation Publisher Pubmed



Golmohammadi M¹ ; Ivraghi MS² ; Hasan EK³ ; Huldani H⁴ ; Zamanian MY^{5, 6, 7} ; Rouzbahani S^{8, 9} ; Mustafa YF¹⁰ ; Alhasnawi SS¹¹ ; Alazbjee AAA¹² ; Khalajimoqim F⁷ ; Khalaj F¹³
Source: Clinical and Experimental Nephrology Published:2024

Abstract

Background: Renal ischemia-reperfusion injury (RIRI) is a critical phenomenon that compromises renal function and is the most serious health concern related to acute kidney injury (AKI). Pioglitazone (Pio) is a known agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ). PPAR-γ is a nuclear receptor that regulates genes involved in inflammation, metabolism, and cellular differentiation. Activation of PPAR-γ is associated with antiinflammatory and antioxidant effects, which are relevant to the pathophysiology of RIRI. This study aimed to investigate the protective effects of Pio in RIRI, focusing on oxidative stress and inflammation. Methods: We conducted a comprehensive literature search using electronic databases, including PubMed, ScienceDirect, Web of Science, Scopus, and Google Scholar. Results: The results of this study demonstrated that Pio has antioxidant, anti-inflammatory, and anti-apoptotic activities that counteract the consequences of RIRI. The study also discussed the underlying mechanisms, including the modulation of various pathways such as TNF-α, NF-κB signaling systems, STAT3 pathway, KIM-1 and NGAL pathways, AMPK phosphorylation, and autophagy flux. Additionally, the study presented a summary of various animal studies that support the potential protective effects of Pio in RIRI. Conclusion: Our findings suggest that Pio could protect the kidneys from RIRI by improving antioxidant capacity and decreasing inflammation. Therefore, these findings support the potential of Pio as a therapeutic strategy for preventing RIRI in different clinical conditions. Graphical abstract: Pioglitazone (Pio) plays a protective role in renal ischemia–reperfusion injury (RIRI) by regulating oxidative stress and inflammation responses. In an animal model of RIRI, Pio reduced inflammation, and oxidative stress renal tubule damage through several cellular pathways. It also promotes cell viability and inhibits autophagy. Pioe targets various pathways such as TNF-α, NF-κB signaling systems, KIM-1 and NGAL pathways, and AMPK phosphorylation. (Figure presented.) © The Author(s), under exclusive licence to Japanese Society of Nephrology 2024.