Exploring the Protective Role and Regulation of Prdx6 in Cisplatin‐Induced <scp>AKI</scp>

Cisplatin (CDDP) is a widely used chemotherapeutic agent that induces nephrotoxicity by generating excessive reactive oxygen species (ROS), leading to oxidative stress, inflammation and apoptosis in renal proximal tubular cells. Peroxiredoxin 6 (Prdx6), an antioxidant enzyme, plays a crucial role in maintaining ROS homeostasis by degrading hydroperoxides; however, its role in CDDP-induced acute kidney injury (CIAKI) remains unclear. In this study, a CIAKI model was established using CDDP treatment in vivo (C57BL/6 mice) and in vitro (PTECs) with or without Prdx6 overexpression (Prdx6 OE). CDDP treatment significantly increased ROS levels, while Prdx6 OE attenuated oxidative stress, apoptosis and renal tubular damage. Furthermore, we found that Prdx6 expression was regulated by Nuclear factor erythroid 2-related factor 2 (Nrf2), suggesting a mechanistic link between Nrf2 and Prdx6 in CIAKI. These findings indicate that Prdx6 plays a protective role in CDDP-induced nephrotoxicity by modulating oxidative stress and apoptosis, and highlight its potential as a therapeutic target.