Memantine ameliorates oxaliplatin-induced neurotoxicity via mitochondrial protection

Bioengineered

Bo Jiang¹  Youyu Wang²  Wang Luo³ 

[1] Department of Thoracic Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China;Department of Thoracic Surgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, China;Departments of Respiratory Diseases, Zengcheng Branch of Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China;

关键词: Oxaliplatin;    memantine;    oxidative stress;    mitochondrial dysfunction;    neurotoxicity;   

DOI  :  10.1080/21655979.2022.2026553

来源: DOAJ

【 摘 要 】

Oxaliplatin is an effective chemotherapeutic agent for the treatment of malignant tumors. However, severe oxaliplatin-induced neurotoxicity has been well documented. Memantine is a drug for the management of Alzheimer’s Disease (AD) due to its promising neuroprotective properties. We hypothesize that Memantine possesses a beneficial role against chemotherapy-induced neuronal damages. In this study, we established an oxaliplatin-induced neurotoxicity assay model in human SHSY-5Y neuronal cells and investigated the protective effect of Memantine. We showed that Memantine treatment ameliorated oxaliplatin-elevated intracellular production of reactive oxygen species (ROS), lipid product malondialdehyde (MDA), and NOX-2 expression. Memantine alleviated impairment of the mitochondrial membrane potential and ATP production by oxaliplatin. As a result, Memantine showed a protective role against oxaliplatin-induced cytotoxicity. Moreover, the terminal deoxynucleotidyl Transferase-mediated dUTP nick end labeling (TUNEL) apoptosis assay revealed that Memantine protected oxaliplatin-induced apoptosis through mitigating the ratio of Bax/Bcl-2 and Caspase-3 cleavage. We concluded Memantine ameliorated the neurotoxicity of oxaliplatin in a mitochondrial-dependent pathway.

【 授权许可】

Unknown