Abstract Nausea and vomiting are commonly reported side effects of long-term linezolid therapy, which is indispensable for tuberculosis and osteoarticular infections. Since the mechanism underlying the development of nausea and vomiting during linezolid treatment is unknown, this study aimed to explore the mechanisms by focusing on the monoamine oxidase-inhibiting effect of linezolid. In vitro serotonin release assays were performed using QGP-1 cells as a surrogate for enterochromaffin cells exposed to linezolid, the monoamine oxidase inhibitor clorgyline, and the known emetogenic agent cisplatin. Serotonin concentrations in the solutions were measured using an enzyme-linked immunosorbent assay. Clorgyline and cisplatin were administered simultaneously with linezolid to elucidate the serotonin release mechanism and confirm the synergistic effects. The intracellular Ca2+assays using Fura‑2 were also performed to assess whether serotonin release is mediated by Ca2+‑dependent exocytosis. Linezolid exposure significantly increased serotonin release from QGP-1 cells in concentration- and time-dependent manners. Serotonin release also increased in the clorgyline exposure group, and the release of serotonin in the linezolid/clorgyline co-exposure group was higher than that in the single-exposure groups. In contrast, no significant serotonin release or synergistic effects were observed in the cisplatin/linezolid-exposed groups. The Ca2+assays demonstrated that linezolid exposure did not change intracellular Ca2+levels. Serotonin release was observed when QGP-1 cells were exposed to linezolid, an effect similar to that observed with the potent monoamine oxidase A inhibitor clorgyline. Furthermore, the Ca2+assays indicated that linezolid‑induced serotonin release occurs independently of Ca2+‑dependent exocytosis.
Tsutsumi et al. (Mon,) studied this question.