Agomelatine reduces brain, kidney and liver oxidative stress but increases plasma cytokine production in the rats with chronic mild stress-induced depression
Agomelatine reduces brain, kidney and liver oxidative stress but increases plasma cytokine production in the rats with chronic mild stress-induced depression
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DOI：
10.1007/s11011-016-9874-2
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发表时间：
2016-12-01
影响因子：
3.6
通讯作者：
Unal, Gulin Ozdamar
中科院分区：
文献类型：
--
作者：
Demirdas, Arif;Naziroglu, Mustafa;Unal, Gulin Ozdamar
阿戈美拉汀（AGOM）作为一种抗抑郁药，同时作为褪黑激素受体激动剂和选择性血清素受体拮抗剂。作为一种有效的褪黑素衍生抗氧化剂，AGOM可能调节抑郁诱导的脑、肾和肝脏的脂质过氧化和促炎细胞因子。本研究探讨AGOM是否对实验性抑郁诱导的慢性轻度应激（CMS）抑郁症大鼠的脑、肾、肝氧化应激和血浆细胞因子产生有保护作用。36只大鼠被分为四组。第一组作为未经治疗的对照组。第二组给予AGOM治疗4周。第三组以慢性轻度应激（CMS）诱导抑郁4周。第四组给予AGOM 40 mg/kg加CMS治疗，疗程4周。肝和肾脂质过氧化水平在CMS组较高，而AGOM组较低。AGOM和AGOM + CMS处理增加了CMS组脑、肾和肝脏中谷胱甘肽过氧化物酶活性降低和谷胱甘肽水平降低。4组小鼠脑、肾、肝中β -胡萝卜素、维生素A、维生素E浓度均未受CMS和AGOM处理的影响。然而，CMS和AGOM组血浆中tnf - α、白细胞介素(IL)-1 β和IL-4水平较高，且AGOM + CMS治疗后其水平进一步升高。综上所述，AGOM通过调节谷胱甘肽浓度和谷胱甘肽过氧化物酶活性，对实验性抑郁症诱导的脑、肾和肝脏氧化损伤具有保护作用。然而，AGOM处理可增加血浆细胞因子的产生。
Agomelatine (AGOM) as an antidepressant acts both as a melatonin-receptor agonist and a selective serotonin-receptor antagonist. As a potent melatonin derived antioxidant, AGOM might modulate depression-induced lipid peroxidation and pro-inflammatory cytokines in brain, kidney and liver. The present study explores whether AGOM protects against experimental depression-induced brain, kidney and liver oxidative stress, and plasma cytokine production in rats with chronic mild stress (CMS)-induced depression. Thirty-six rats were divided into four groups. The first group was used as an untreated control. The second group received AGOM for 4 weeks. The third group was exposed to chronic mild stress (CMS) of 4 weeks for induction depression. The fourth group received 40 mg/kg AGOM and CMS for 4 weeks. Liver and kidney lipid peroxidation levels were high in the CMS group although they were low in AGOM treatments. AGOM and AGOM + CMS treatments increased the lowered glutathione peroxidase activity and reduced glutathione levels in brain, kidney and liver of CMS group. beta-carotene, vitamin A and vitamin E concentrations in the brain, kidney and liver of the four groups were not changed by CMS and AGOM treatments. However, plasma TNF-alpha, interleukin (IL)-1 beta, and IL-4 levels were high in the CMS and AGOM group and their levels were further increased by the AGOM + CMS treatment. In conclusions, AGOM induced protective effects against experimental depression-induced brain, kidney, and liver oxidative injuries through regulation of the glutathione concentrations and glutathione peroxidase activity. However, plasma cytokine productions were increased by the AGOM treatment.