Acyclovir inhibits rat liver tryptophan-2,3-dioxygenase and induces a concomitant rise in brain serotonin and 5-hydroxyindole acetic acid levels
Acyclovir inhibits rat liver tryptophan-2,3-dioxygenase and induces a concomitant rise in brain serotonin and 5-hydroxyindole acetic acid levels
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DOI：
10.1007/s11011-008-9095-4
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发表时间：
2008-07
影响因子：
3.6
通讯作者：
A. Müller;S. Daya
中科院分区：
文献类型：
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作者：
A. Müller;S. Daya
脑病毒性疾病可引起神经递质合成和代谢的变化。在实验性单纯疱疹病毒性脑炎中，脑5-羟色胺减少，而其主要代谢产物5-羟基吲哚乙酸和周转增加。已经确定，脑单胺、血清素和去甲肾上腺素水平的降低可能导致临床抑郁症的症状，这增加了这种情况在单纯疱疹脑炎中普遍存在的可能性。肝脏色氨酸-2，3-双加氧酶活性与脑5-羟色胺水平之间存在反比关系，5-羟色胺和去甲肾上腺素水平之间存在相互依赖性。本研究的目的是确定用于治疗单纯疱疹病毒性脑炎的抗病毒药物阿昔洛韦对体外和体内大鼠肝脏色氨酸-2，3-双加氧酶活性以及对大鼠前脑5-羟色胺、5-羟基吲哚乙酸和去甲肾上腺素水平的影响。结果表明，在体外和体内，无环鸟苷抑制色氨酸-2，3-双加氧酶的活性，同时升高血清素和5-羟吲哚乙酸水平。然而，阿昔洛韦减少5-羟色胺转化为5-羟基吲哚乙酸，对去甲肾上腺素水平没有任何影响。看来，阿昔洛韦可能有可能减少单纯疱疹病毒性脑炎抑郁症的临床症状。然而，5-羟色胺转化为5-羟基吲哚乙酸的更大周转率可能被5-羟色胺转化为5-羟基吲哚乙酸所掩盖，这需要进一步研究。
Viral diseases of the brain may induce changes in neurotransmitter synthesis and metabolism. In experimental herpes simplex encephalitis, brain serotonin is reduced, whilst it’s major metabolite, 5-hydroxyindole acetic acid and turnover is increased. It is well established that reduced levels of brain monoamines, serotonin and norepinephrine may contribute to the symptoms of clinical depression, which raises the possibility that this condition is prevalent in herpes simplex encephalitis. An inverse relationship exists between liver tryptophan-2,3-dioxygenase activity and brain serotonin levels and there is an interdependency between serotonin and norepinephrine levels. The aim of this study is to determine the effect of acyclovir, an antiviral used in the treatment of herpes simplex encephalitis, on rat liver tryptophan-2,3-dioxygenase activityin vitroandin vivoas well as on rat forebrain serotonin, 5-hydroxyindole acetic acid and norepinephrine levels. The results show that acyclovir inhibits tryptophan-2,3-dioxygenase activityin vitroandin vivo, with a concomitant rise in serotonin and 5-hydroxyindole acetic acid levels. However, acyclovir reduces the turnover of serotonin to 5-hydroxyindole acetic acid, without any effect on norepinephrine levels. It appears that acyclovir may have the potential to reduce the clinical symptoms of depression in herpes simplex encephalitis. However, a greater turnover of serotonin to 5-hydroxyindole acetic acid could possibly be masked by conversion of serotonin to 5-hydroxytryptophol, which needs to be investigated further.