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3,4-Methylenedioxymethamphetamine causes cytotoxicity on 661W cells through inducing macrophage polarization.

Xin Liu, Li-Hui Zhan, Xiao-Hong Sun, Tao Zhang, Zhi-Li Liu, Xiao-Fang Liang, Fei Zhao, Fang Liu, Guang Zeng, Chun-Sheng Luan

Cutaneous and Ocular Toxicology June 2018 DOI: 10.1080/15569527.2017.1359838 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics In vitro cell co-culture study Peer reviewed
Population 661W photoreceptor cells and RAW264.7 macrophages in co-culture
Intervention MDMA
Topics MDMA
Keywords 3,4-methylenedioxymeth-amphetamine 661w cells Inflammatory response Macrophage Photoreceptor cell damage
Key points MDMA at a nontoxic concentration induced macrophages to adopt an M1 polarization state, increasing pro-inflammatory cytokine release and M1-related gene and protein expression, with a phenotype and secretion pattern comparable to IFNγ/LPS stimulation. This macrophage activation was associated with cytotoxicity to co-cultured 661W photoreceptor cells, which the authors propose as an indirect mechanism for photoreceptor damage from MDMA abuse.

Abstract

The abuse of 3,4-methylenedioxymethamphetamine (MDMA), a psychedelic drug, can lead to a variety of disorders in neural system, including the death of retinal neural cells. MDMA at lower doses does not cause obvious cytotoxicity to photoreceptor cells, indicating potential indirect mechanisms which have not yet been elucidated. This study investigated the effect of MDMA at nontoxic concentration on macrophage activation state and its resultant toxicity to photoreceptor cells. Using a co-culture system, cytotoxicity was caused by MDMA on 661W cells after co-culturing with RAW264.7 macrophage. Results showed that MDMA induced the macrophages to M1 polarization, releasing more pro-inflammatory cytokines, upregulating the M1-related gene and protein expression. The phenotype, secretion pattern, and cytotoxicity of the macrophages treated by MDMA are comparable to those of the ones stimulated by IFNγ and LPS. Our study demonstrated that MDMA promoted macrophage polarization to M1 and induced inflammatory response, providing the scientific rationale for the photoreceptor cell damage caused by the MDMA abuse.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

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