Indole-3-carboxaldehyde alleviates cisplatin-induced acute kidney injury in mice by improving mitochondrial dysfunction via PKA activation

Abstract

Cisplatin (DDP) is widely used in the treatment of cancer as a chemotherapeutic drug. However, its severe nephrotoxicity limits the extensive application of cisplatin, which is characterized by injury and apoptosis of renal tubular epithelial cells. This study aimed to reveal the protective effect and its underlying mechanism of Indole-3-carboxaldehyde (IC) against DDP-induced AKI in mice and NRK-52E cells pretreated with PKA antagonist (H-89). Here, we reported that IC improved renal artery blood flow velocity and renal function related indicators, attenuated renal pathological changes, which were confirmed by the results of HE staining and PASM staining. Meanwhile, IC inhibited the levels of inflammatory factors, oxidative stress, CTR1, OCT2, and the levels of autophagy and apoptosis. Mitochondrial dysfunction was significantly improved as observed by TEM. To clarify the potential mechanism, NRK-52E cells induced by DDP was used and the results proved that H-89 could blocked the improvement with IC effectively in vitro. Our findings showed that IC has the potential to treat cisplatin-induced AKI, and its role in protecting the kidney was closely related to activating PKA, inhibiting autophagy and apoptosis, improving mitochondrial function, which could provide a theoretical basis for the development of new clinical drugs.