Protective Effects of Maropitant in Chemotherapy-Induced Cognitive Impairment Caused by Methotrexate
Durmuş Ali Aslanlar1, Fatma Nur Bilgiç21Department of Medical Pharmacology, Faculty of Medicine, Necmettin Erbakan University, Konya, Türkiye, 2Department Veterinary Physiology, Faculty of Veterinary Medicine, Aksaray University, Aksaray, Türkiye
Objectives: This study aimed to investigate whether prophylactic maropitant (MAR) administration can attenuate methotrexate (MTX)-induced cognitive impairment and related hippocampal molecular alterations. Methods: Twenty-eight 10-week-old male BALB/c mice were randomly assigned to four groups (n=7): control, MTX, MTX+MAR, and MAR. MTX was administered intraperitoneally at 40 mg/kg 24 hours before behavioral testing. Maropitant was given subcutaneously at 10 mg/kg two days before and one hour before MTX administration. Cognitive function was evaluated using the novel object recognition (NOR) test. After behavioral assessment, animals were sacrificed, hippocampal tissues were collected, and levels of TLR4, amyloid beta (A?1–42), tau, and brain-derived neurotrophic factor (BDNF) were quantified using ELISA. Results: MTX administration significantly impaired cognitive performance, evidenced by reduced hippocampal BDNF levels and increased TLR4, tau, and A?1–42 levels (p<0.001), along with a marked decrease in the NOR discrimination index (p<0.001). Maropitant treatment effectively prevented these MTX-induced molecular and behavioral alterations, maintaining all parameters near control levels and significantly improving outcomes compared to the MTX group. Conclusion: Prophylactic maropitant administration protected against MTX-induced acute cognitive impairment by modulating hippocampal inflammatory and neurodegenerative pathways, suggesting NK1 receptor antagonism as a promising preventive strategy for chemotherapy-related cognitive dysfunction. Keywords: Cognitive Impairment, Maropitant, Methotrexate
Cite This Article
Aslanlar D, Bilgiç F. Protective Effects of Maropitant in Chemotherapy-Induced Cognitive Impairment Caused by Methotrexate. EJMI. 2026; 10(1): 90-97
Corresponding Author: Durmuş Ali Aslanlar