Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels
Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels
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DOI：
10.1016/j.lfs.2006.07.028
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发表时间：
2006-11-10
期刊：
影响因子：
6.1
通讯作者：
Daya, S.
中科院分区：
文献类型：
--
作者：
Dairam, A.;Antunes, E. M.;Daya, S.
肝色氨酸2,3-双加氧酶（Hepatic tryptophan 2,3-dioxygenase， TDO）是色氨酸分解代谢的限速酶之一，在调节色氨酸进入相关代谢途径的生理通量中起重要作用。在本研究中，我们测定了非甾体抗炎药托美汀和舒林酸对大鼠肝脏TDO活性的影响以及随后海马和纹状体神经递质水平的变化。用高效液相色谱法测定松果体产生褪黑素的量。大鼠给予托美汀或舒林酸（5mg /kg/bd，连续5天）显著抑制肝脏TDO活性。结果表明，托尔美汀和舒林酸增加海马体内的促肽水平的同时，这些药物也显著降低纹状体中的多巴胺水平。托尔美汀增加了松果体产生的褪黑激素的数量，而不是舒林达克。这项研究的结果表明，虽然托美汀和舒林酸可能对抑郁症患者有益，但这些药物也有可能对患有神经系统疾病（如帕金森病）的患者产生不良影响。(c) 2006爱思唯尔公司版权所有。
Hepatic tryptophan 2,3-dioxygenase (TDO) is one of the rate-limiting enzymes in tryptophan catabolism and plays an important role in regulating the physiological flux of tryptophan into relevant metabolic pathways. In this study, we determined the effect of the non-steroidal anti-inflammatory agents, tolmetin and sulindac, on rat liver TDO activity and the subsequent changes in the hippocampal and striatal neurotransmitter levels. The amount of melatonin produced by the pineal gland was also measured using high performance liquid chromatography (HPLC). Treatment of rats with tolmetin or sulindac (5 mg/kg/bd for 5 days) significantly inhibited liver TDO activity. The results show that whilst tolmetin and sulindac increase scrotonin levels in the hippocampus, these agents also significantly reduce dopamine levels in the striatum. Tolmetin, but not sulindac, increased the amount of melatonin produced by the pineal gland. The results of this study suggest that whilst tolmetin and sulindac may be beneficial for patients suffering from depression, these agents also have the potential to induce adverse effects in patients suffering with neurological disorders such as Parkinson's disease. (c) 2006 Elsevier Inc. All rights reserved.