South Korea: A recent study published in Frontiers in Medicine has shown oxypurinol to be protective against renal ischemia/reperfusion (I/R) injury by reducing inflammation, oxidative stress, and apoptosis via HO-1 induction. The findings suggest its potential in preventing ischemic acute kidney injury (AKI).
Renal ischemia/reperfusion injury is defined as the restriction of blood supply to the kidney (ischemia) followed by blood flow restoration and reoxygenation (reperfusion). It is a major cause of acute kidney injury by increasing inflammatory responses, oxidative stress, and tubular cell death. Oxypurinol, an active metabolite of allopurinol, is a potent antioxidant and anti-inflammatory agent.

Hye Bin Kang, Pukyong National University, Busan, Republic of Korea, and colleagues aimed to investigate the therapeutic potential and underlying mechanism of oxypurinol in ischemic AKI, C57BL/6 male mice were intraperitoneally injected with oxypurinol and subjected to renal I/R or sham surgery.
The researchers revealed the following findings:
Oxypurinol-treated mice had lower levels of plasma creatinine and blood urea nitrogen and tubular damage (hematoxylin-and-eosin staining) compared to vehicle-treated mice after renal I/R injury.
Oxypurinol treatment reduced oxidative stress (i.e., 4-HNE, heme oxygenase-1 [HO-1], 8-OHdG expression, and Catalase mRNA induction), kidney inflammation (i.e., neutrophil infiltration and MIP-2 mRNA induction), and apoptosis (i.e., TUNEL or cleaved caspase-3-positive renal tubular cells), compared to vehicle-treated mice.
Mechanistically, oxypurinol-induced protein expressions of HO-1, which is a critical cytoprotective enzyme during ischemic AKI, and oxypurinol-mediated protection against ischemic AKI was eliminated by pretreatment with tin protoporphyrin IX, an HO-1 inhibitor.
"Our renal I/R model is a leading cause of perioperative acute kidney injury in various clinical settings such as vascular, hepatic and cardiac surgeries, and kidney transplantation," the researchers wrote. "So, it is possible to adapt kidney to renal ischemia/reperfusion injury before those clinical surgeries by preconditioning such as remote organ ischemia, short ischemia, and treatment of pharmacological drug including HO-1 activators."
"Therefore, the findings suggest that oxypurinol-mediated preconditioning via HO-1 induction protects ischemic AKI rather than recovers from ischemic AKI by attenuating apoptosis, necrosis, inflammation, and oxidative damage after I/R, indicating that oxypurinol and its underlying mechanism may be a potential drug for preventing ischemic AKI," they concluded.
Reference:
Kang, H. B., Lim, C. K., Kim, J., & Han, S. J. (2023). Oxypurinol protects renal ischemia/reperfusion injury via heme oxygenase-1 induction. Frontiers in Medicine, 10, 1030577. https://doi.org/10.3389/fmed.2023.1030577