| 摘要(英) | 2C-T-2 (2,5–dimethoxy–4–ethylthio- phenethylamine), a psychoactive drug, is a ring-substituted phenethylamine derivative that exerts psychological effects including changes in mood, cognition, and behavior. It had been reported that psychoactive drugs caused the health problems if there were abused intake. The previously studies indicated that oral intake 2C-T-2 suppressed the nitric oxide production of mitogen-stiumated splenocytes in mice. However, little information is available concerning its bioactivity and immunomodulatory activity. In this study, the metabolic kinetic and immunomodulatory effects of 2C-T2 after single or repeated oral intake are examined and characterized used the mice animal model. In addition, the neuroendocrine-mediated mechanism(s) of 2C-T-2-induced immunosuppression was also examined. Results indicated that the level of 2C-T-2 in the peripheral blood was firstly detected at 30 minutes after intake, and 6 hours later, the level of 2C-T-2 was metabolic clear and less than detectable amount. In parallel, 2C-T-2 oral intake also increased the level of corticosterone in blood plasma. The results of single intake 2C-T-2 on immune activities indicated that 2C-T-2 induced the decrease the distribution of T, B, and NK cell populations in peripheral blood. And the ability of phagocytosis in leukocytes was suppressed significantly after 2C-T-2 oral intake 6 hours. 2C-T-2 also induced the suppression of mitogen-stimulated proliferation and nitric oxide in spleen and thymus. In addition, the production of IL-1β, IL-6, TNF-α, IFN-γ, IL-4, and IL-10 cytokines from LPS or Con A-stimulated splenocytes were significantly decreased after 2C-T-2 oral intake. However, 2C-T-2 intake significantly increased the IL-2 and TGF-β1 production. Repeated 2C-T-2 intake induced the immunosuppression on production of nitric oxide, IL-1β, IL-6, TNF-α, IL-4, IL-10, and TGF-β1, but no change on leukocytes subpopulation number, proliferation and production of IL-2 and IFN-γ. Furthermore, in this study, we observed that in vitro exposure to 2C-T-2 did not alter LPS-stimulated nitric oxide production. This data indicate that the ability of 2C-T-2 to suppress the production of nitric oxide and cytokine production is not due to a direct action on immune cells. Interestingly, administrated nodolol, a β-adrenoceptor blockade, or epinephrine attenuated the decrease in nitric oxide production induced by 2C-T-2 oral intake. In summary, these data demonstrate that 2C-T-2 intake induce the suppression effect on immune activities of mice. However, further studies are needed to elucidate the exact mechanisms that underlie 2C-T-2 induced suppression of nitric oxide and cytokine production. |
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