Programa de Pós-graduação em Bioquímica (PPGBioq), Universidade Federal do Pampa (Unipampa), Campus Uruguaiana, BR 472 KM 582, Caixa Postal 118, CEP 97500-970 RS, Brazil.
Life Sci. 2013 Sep 17;93(9-11):393-400. doi: 10.1016/j.lfs.2013.07.024. Epub 2013 Aug 2.
The study investigated the antidepressant-like effect and acute toxicity of 4-phenyl-1-(phenylselanylmethyl)-1,2,3-triazole (Se-TZ), an organoselenium-containing heterocycle compound in mice.
The antidepressant-like effect of Se-TZ (1-50mg/kg) and its mechanism of action, was analyzed in the tail suspension test (TST) in male C57BL/6J mice. Additionally, the levels of the monoamines and their metabolites in cerebral cortex and hippocampus were analyzed by high-performance liquid chromatography. To investigate the potential acute toxicity caused by Se-TZ, the mice received a single oral dose of Se-TZ (1-50mg/kg), and after 72h were performed the assays.
The Se-TZ (5-50mg/kg) significantly reduced immobility time in TST without altering locomotor and exploratory activities. The antidepressant-like effect of Se-TZ (25mg/kg) in the TST was prevented by pre-treatment of mice with SCH23390, sulpiride and methysergide, but not with prazosin, yohimbine and propranolol. Se-TZ, increased monoamine neurotransmitters dopamine and serotonin levels in the cerebral cortex and hippocampus, whereas norepinephrine turnover was not changed. This study also demonstrated that the Se-TZ, did not cause the acute toxicity in biochemical markers hepatic and renal investigated. The results evidenced that exposure to Se-TZ caused a significant increase in the catalase (CAT) activity in the cerebral cortex and hippocampus, however the glutathione S-transferase (GST) activity increased only in the cerebral cortex.
These results suggest that Se-TZ demonstrated antidepressant-like effect, mediated via the central dopaminergic and serotoninergic neurotransmitter systems which may be of interest as a therapeutic agent for the treatment of depressive disorders.
本研究旨在探讨含硒杂环化合物 4-苯基-1-(苯硒基甲基)-1,2,3-三唑（Se-TZ）在小鼠体内的抗抑郁样作用及其急性毒性。
采用雄性 C57BL/6J 小鼠悬尾试验（TST）分析 Se-TZ（1-50mg/kg）的抗抑郁样作用及其作用机制，同时采用高效液相色谱法分析大脑皮质和海马中单胺类神经递质及其代谢产物的水平。为了研究 Se-TZ 可能引起的急性毒性，小鼠单次口服 Se-TZ（1-50mg/kg），72h 后进行各项检测。
Se-TZ（5-50mg/kg）可显著减少 TST 中小鼠不动时间，而不改变其运动和探索活动。Se-TZ（25mg/kg）在 TST 中的抗抑郁样作用可被 SCH23390、sulpiride 和 methysergide 预处理所阻断，但不能被 prazosin、yohimbine 和 propranolol 所阻断。Se-TZ 增加了大脑皮质和海马中单胺神经递质多巴胺和 5-羟色胺的水平，而去甲肾上腺素的转化率没有改变。本研究还表明，Se-TZ 未引起所研究的生化标志物肝和肾的急性毒性。结果表明，暴露于 Se-TZ 可导致大脑皮质和海马中过氧化氢酶（CAT）活性显著增加，而谷胱甘肽 S-转移酶（GST）活性仅在大脑皮质中增加。
这些结果表明，Se-TZ 表现出抗抑郁样作用，这可能与中枢多巴胺能和 5-羟色胺能神经递质系统有关，作为治疗抑郁障碍的治疗剂可能具有一定的应用价值。
