Leonurine attenuates cisplatin nephrotoxicity by suppressing the NLRP3 inflammasome, mitochondrial dysfunction, and endoplasmic reticulum stress

Purpose Cisplatin has been widely accepted as an effective chemotherapy drug with various side effects, including nephrotoxicity. The mechanisms of cisplatin-induced acute kidney injury (AKI) are complex, and there are limited renoprotective approaches. Leonurine is the main active compound of a Chinese herb and has recently been reported to have a protective effect on the kidneys. This study aimed to verify the renoprotective effect of leonurine in attenuating cisplatin-induced AKI and explore the potential associated mechanisms. Methods C57BL/6 mice were divided into four groups (Sham, Cisplatin, Leonurine, and Cisplatin + Leonurine). Mice in the leonurine-treated groups were pretreated with a daily intraperitoneal injection of 25 mg/kg leonurine. AKI was induced by injecting cisplatin once intraperitoneally at 20 mg/kg body weight. Mice were killed on day 5. Kidney injury was assessed using a serum biochemical and histological assay. Apoptosis was evaluated using a terminal deoxyribonucleotide transferase-mediated dUTP nick-end labeling (TUNEL) staining assay and Western blot. Antioxidant enzymes were detected using commercial kits. The improvement in inflammasome activation, mitochondrial dysfunction, and endoplasmic reticulum stress (ERS) were assessed by polymerase chain reaction (PCR) and Western blot, respectively. Results Leonurine treatment improved kidney function by preventing renal tubular injury and apoptosis. Expression of nucleotide-binding leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome components and inflammatory cytokines, mitochondrial dysfunction, and ERS were all alleviated by leonurine. Conclusion The results indicate that leonurine plays a protective role in cisplatin-induced AKI and may represent an effective multi-targeted intervention strategy.

Automated summary

This study confirmed the renoprotective effect of leonurine in attenuating cisplatin-induced AKI and explored the potential mechanisms associated with it.