2025/11/01 by Roberta Foresti, Sandra Shurey, Qiyue Mao +3 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Heme Oxygenase-1 and Carbon Monoxide #Hemoglobin structure and function #Neonatal Health and Biochemistry
paper · pdf · doi:10.14814/phy2.70666
openalex publication_date 2025/11/01 · openalex created_date 2025/11/15 · openalex updated_date 2026/07/23
Carbon monoxide (CO), a gas endogenously produced in mammalian tissues, exerts vasodilatory, anti-ischemic, and anti-inflammatory effects. These properties have prompted the development of CO-releasing molecules (CO-RMs) for therapeutic purposes. Among this class of compounds is CORM-A1, a boron-based carboxylic acid, which generates controlled amounts of CO under physiological conditions. In this proof-of-principle study we explored the potential of CORM-A1 to protect kidneys from warm ischemia and reperfusion (WI/R) injury in rat and swine models. We found that intravenous administration of CORM-A1 significantly increased blood carboxyhemoglobin (COHb) levels while facilitating CO accumulation in renal tissue, thus confirming its ability to deliver CO to peripheral organs. In rats subjected to 45- and 60-min WI/R, administration of CORM-A1 improved renal function at reperfusion, as shown by decreased serum creatinine and urea levels. Histopathological analysis revealed substantial protection against tubular damage, cell infiltration, and inflammation, especially after 60-min ischemia. Protection was dose-dependent, with higher doses offering enhanced effects. In a swine kidney auto-transplantation model, CORM-A1 significantly improved graft function, reduced fibrosis and necrosis, and extended graft survival. These findings position CORM-A1 as a promising CO prodrug, with translational relevance for clinical applications in kidney transplantation and other ischemia-related conditions.