Lansoprazole promotes cisplatin-induced acute kidney injury via enhancing tubular necroptosis
Abstract
Acute kidney injury (AKI) is the main obstacle that limits the use of cisplatin in cancer treatment. Proton pump inhibitors (PPIs), the most commonly used class of medications for gastrointestinal complications in cancer patients, have been reported to cause adverse renal events. However, the effect of PPIs on cisplatin‐induced AKI remains unclear. Herein, the effect and mechanism of lansoprazole (LPZ), one of the most frequently prescribed PPIs, on cisplatin‐induced AKI were investigated in vivo and in vitro. C57BL/6 mice received a single intraperitoneal (i.p.) injection of cisplatin (18 mg/kg) to induce AKI, and LPZ (12.5 or 25 mg/kg) was administered 2 hours prior to cisplatin administration and then once daily for another 2 days via i.p. injection. The results showed that LPZ significantly aggravated the tubular damage and further increased the elevated levels of serum creatinine and blood urea nitrogen induced by cisplatin. However, LPZ did not enhance cisplatin‐induced tubular apoptosis, as evidenced by a lack of significant change in mRNA and protein expression of Bax/Bcl‐2 ratio and TUNEL staining. Notably, LPZ increased the number of necrotic renal tubular cells compared to that by cisplatin treatment alone, which was further confirmed by the elevated necroptosis‐associated protein expression of RIPK1, p‐RIPK3 and p‐MLKL. Furthermore, LPZ deteriorated cisplatin‐induced inflammation, as revealed by the increased mRNA expression of pro‐inflammatory factors including,…
Read the paper
Related studies
- The Prediction of the In Vitro Release Curves for PLGA-Based Drug Delivery Systems with Neural Networks
- Promising Ursolic Acid as a Novel Antituberculosis Agent: Current Progress and Challenges
- Proof of principle concept for the analysis and functional prediction of rare genetic variants in the CYP2C19 and CYP2D6 genes
- Fabrication, characterization, and docking studies of furosemide-loaded nanosponges using the emulsion solvent diffusion method
- The Effect of Concomitant Administration of Proton Pump Inhibitors on the Pharmacokinetics of CDK4/6 Inhibitors in Rats: Implications for the Evaluation of Hepatic and Transporter-Mediated Drug–Drug Interactions
- Mining the Metabolic Capacity of Clostridium sporogenes Aided by Machine Learning
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.