3.8 Leonurine suppresses lipid peroxidation and ferroptosis in CI-AKI
Next, we assessed the effects of leonurine on cisplatin-induced lipid peroxidation and ferroptosis in vivo. Compared to the control, cisplatin significantly increased the MDA content and decreased the GSH and SOD contents in the kidney, while leonurine obviously reversed the above changes (Fig. 8A-C). In addition, the protein levels of GPX4 and xCT were significantly downregulated by cisplatin treatment but dose-dependently restored by leonurine treatment. Moreover, the protein levels of Nrf2 and its regulated downstream antioxidases NQO1 and HO-1 were activated by leonurine treatment (Fig. 8D-F). Similar to the protein levels, the mRNA levels of GPX4 and xCT were decreased in the renal tissues of the model group. Interestingly, leonurine treatment significantly increased the transcript levels of GPX4 and xCT (Fig. 8G-H). Moreover, electron microscopic observations revealed mitochondrial damage in renal tissue cells of the model group, manifested as mitochondrial rupture and disappearance of mitochondrial cristae, and leonurine treatment significantly alleviated this damage (Fig. 8I).