Effect of phenelzine and serotonin on RAW264.7 macrophage cell viability

Background: Serotonin is a neurotransmitter with extensive physiological effects on the Central Nervous System (CNS) and various biological functions, including the regulation of immunity through 5-hydroxytryptamine receptors (5-HTRs) expressed by immune cells such as macrophages. Phenelzine, a medication used in managing treatment-resistant depression, acts as a potent monoamine oxidase inhibitor (MAOI). This enzyme metabolizes serotonin into 5-hydroxyindoleacetic acid (5-HIAA). Antidepressants e.g., Phenelzine may benefit patients with neurological disorders, who can also be prone to immune-related conditions and cancer. This study aimed to investigate the cytotoxic effects of Phenelzine, serotonin, and 5-HIAA on RAW264.7 macrophages. Methods: We cultured RAW264.7 macrophages as a model that could express transporter receptors and enzymes associated with serotonin. We utilized MTT assay to evaluate the survival of RAW264.7 cells exposed to different concentrations of Phenelzine, serotonin, and 5-HIAA, pre-treated with lipopolysaccharide (LPS). Results: Our findings revealed that LPS-treated RAW264.7 cells exhibited increased resistance to the cytotoxic effects of Phenelzine. Treatment with serotonin resulted in a concentration-dependent increase in RAW264.7 cell proliferation. In contrast, 5-HIAA did not significantly impact cell viability. Conclusion: The present study reveals the effect of Phenelzine and serotonin on viability of RAW264.7 macrophages, particularly in the context of inflammation. It demonstrates increased resistance to the cytotoxic effects of Phenelzine in RAW264.7 cells treated with LPS. Our study contributes to a broader understanding of the potential systemic impacts of antidepressant medications and the intricate interplay between the serotonergic system and immune responses.