Neuroprotective effect of lansoprazole against cisplatin-induced brain toxicity: Role of Nrf2/ARE and Akt/P53 signaling pathways

Cisplatin is a chemotherapeutic agent usually used in treating different patterns of malignancies. One of the significant apparent complications of cisplatin chemotherapy is brain toxicity. The present study was conducted to evaluate the protective effects of lansoprazole on cisplatin-induced cortical intoxication. Thirty-two rats were allocated into four groups (8 rats/group); group I: received only a vehicle for 10 days, group II: lansoprazole was administered (50 mg/kg) via oral gavage for 10 days, group III: On 5th day of the experiment, rats were given cisplatin (10 mg/kg) i.p. once to induce cortical injury. Group IV: rats were given lansoprazole for 5 days before cisplatin and 5 days afterward. Lansoprazole administration significantly improved cisplatin-induced behavioral changes, as evidenced by decreasing the immobility time in forced swimming and open field tests. Besides, lansoprazole improved cortical histological changes, restored cortical redox balance, enhanced Nrf2/ARE expression, cisplatin-induced neuronal apoptosis, and dampened cisplatin inflammation. In addition, lansoprazole modulated cortical Akt/p53 signal. The present work was the first to show that lansoprazole co-administration reduced cortical toxicity in cisplatin-treated rats via multiple signaling pathways. The current findings provided crucial information for developing novel protective strategies to reduce cisplatin cortical toxicity.