Combined Apocynin and Novokinin Treatment Attenuates Renal Damage and Reduces KIM-1 Expression in a Model of Ischemic AKI

Ischemia–reperfusion injury (IRI) of the kidney represents a serious medical issue with complex pathological mechanisms that remain poorly elucidated. The development of ischemic acute kidney injury (AKI) may be mediated by NADPH oxidase and angiotensin II type 2 receptors. The aim of our study was to explore the effects of novokinin (NOV), angiotensin II type 2 receptor (AT2R) agonist and apocynin (APO), an NADPH oxidase inhibitor, on kidney structure and function, as well as the level of oxidative stress in spontaneously hypertensive rats (SHR) with induced IRI. Animals were randomly assigned into five experimental groups: the Sham-operated animals (SHAM) group, the AKI group, and AKI groups receiving APO, NOV, or their combination. Slight improvements in renal function were noted across all treated groups; however, only the combined action of APO + NOV led to a significant decrease in kidney injury molecule-1 (KIM-1) levels and markedly reduced oxidative stress compared with the control AKI group. Our results demonstrate that additively targeting NADPH oxidase and AT2R provides new insights in comparison to individual treatments. These findings suggest a potentially promising new therapeutic strategy for managing IRI and improving outcomes in critically ill patients with AKI.