Cisplatin plays a pivotal role in the chemotherapy treatment of various cancers, but its use is often limited due to its nephrotoxic side effects. Identifying compounds that can mitigate cisplatin-induced nephrotoxicity is therefore of great importance. This study focused on evaluating the protective effects of reserpine against cisplatin-induced acute kidney injury. Reserpine was found to significantly safeguard against kidney damage caused by cisplatin, as indicated by the decreased levels of serum creatinine, blood urea nitrogen, and lactate dehydrogenase induced by cisplatin. Moreover, reserpine improved kidney histology damage caused by cisplatin treatment, with hematoxylin-eosin and periodic acid-Schiff staining revealing notable recovery from renal injury. Mechanistically, reserpine mitigated oxidative stress triggered by cisplatin and exhibits the ability to inhibit ferroptosis both in vivo and in vitro. Additionally, reserpine blocked the activation of the cGAS/STING signaling pathway and the subsequent expression of inflammatory genes, thus reducing inflammation-driven kidney damage. In summary, the findings suggest that reserpine offers a promising new strategy for preventing nephrotoxicity induced by cisplatin.

Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation. In recent years, certain isoforms of glutathione-S-transferases (GSTs) have been identified that may play a key role in regulating ferroptosis. Previous study demonstrated that the NRF2/GSH/GST/RLIP76 and MRP1 axis acts as an independent anti-ferroptosis pathway. Furthermore, this study evaluated the therapeutic potential of mifepristone (RU486) for mitigating acetaminophen (APAP)-induced liver injury in vivo. However, different types of GSTs may have opposite effects, with some inhibiting ferroptosis while others promote it. In addition, GST shows great potential as a biomarker in a wide range of diseases and its activity is strongly associated with renal disease, general anesthesia toxicity, inflammatory diseases, and cancer. Moreover, changes in the GST gene can increase the risk of numerous diseases. Notably, blood levels of GST are influenced by multiple factors and need to be thoroughly evaluated when using GST as a biomarker. In conclusion, GST is valuable in ferroptosis regulation and disease diagnosis, and its specific targeted intervention is expected to provide new strategies for the treatment of related diseases.