Biochemistry Department, Faculty of Science, Alexandria University, Alexandria 21511, Egypt.
Biochemistry Department, Faculty of Science, Alexandria University, Alexandria 21511, Egypt.
Life Sci. 2020 Apr 15;247:117427. doi: 10.1016/j.lfs.2020.117427. Epub 2020 Feb 15.
Neuroinflammation can arise from metabolic disturbances accompanying type 2 diabetes mellitus (T2DM) with an implication of indoleamine 2,3-dioxygenase 1 (IDO1). The antioxidant and anti-inflammatory potentials of melatonin (Mel) can amend diabetic complications. Here, we examined the effect of exogenous melatonin on neuroinflammation in high fat diet (HFD)-induced T2DM rats.
Twenty-one adult male Sprague-dawley rats were divided in to three groups: control group: fed commercial standard rat chow, T2DM group: fed with HFD for 16 weeks, and T2DM-Mel group: received HFD for 8 weeks, followed by weekly melatonin treatment (i.p injection 10 mg/kg in saline) for 8 weeks with continuous supply of HFD. After which, animals were submitted to euthanasia for brain and blood samples collection.
In T2DM-Mel group the diabetic profile was ameliorated, and the state of low-grade systemic inflammation was alleviated through lowering serum pro-inflammatory cytokines (TNF-α and IL-6) and leptin while increasing adiponectin. Melatonin improved brain oxidative stress by increasing total antioxidant capacity and reduced glutathione (GSH), whereas malondialdehyde was declined. Melatonin reduced acetylcholinesterase (AChE) activity in blood and brain and its hippocampal expression, also hippocampal inducible nitric oxide synthase (iNOS) expression was reduced, moreover IDO1 hippocampal expression was declined, furthermore recovered neuronal morphology following melatonin treatment was also clearly viewed in the hippocampus under the light microscope in T2DM-Mel rats.
Melatonin can be considered as a promising solution in preventing neuroinflammation development in T2DM owing to its ability to render the oxidative stress and accompanied low-grade systemic inflammation.
神经炎症可能源于 2 型糖尿病（T2DM）伴有的代谢紊乱，其涉及吲哚胺 2,3-双加氧酶 1（IDO1）。褪黑素（Mel）的抗氧化和抗炎潜力可以改善糖尿病并发症。在这里，我们研究了外源性褪黑素对高脂肪饮食（HFD）诱导的 T2DM 大鼠神经炎症的影响。
21 只成年雄性 Sprague-Dawley 大鼠分为三组：对照组：喂食商业标准大鼠饲料；T2DM 组：喂食 HFD16 周；T2DM-Mel 组：喂食 HFD8 周，随后每周用 Mel（腹腔注射 10mg/kg 生理盐水）治疗 8 周，同时持续供应 HFD。之后，动物被安乐死以收集大脑和血液样本。
在 T2DM-Mel 组中，糖尿病特征得到改善，通过降低血清促炎细胞因子（TNF-α和 IL-6）和瘦素水平，同时增加脂联素水平，缓解了低度全身炎症状态。褪黑素通过增加总抗氧化能力和还原型谷胱甘肽（GSH）来改善大脑氧化应激，同时降低丙二醛水平。褪黑素降低了血液和大脑中的乙酰胆碱酯酶（AChE）活性及其海马表达，也降低了海马诱导型一氧化氮合酶（iNOS）表达，此外，褪黑素还降低了海马 IDO1 表达。在 T2DM-Mel 大鼠的海马体中，在光镜下可以清楚地观察到褪黑素治疗后神经元形态得到恢复。
由于褪黑素能够减轻氧化应激和伴随的低度全身炎症，因此可以被认为是预防 T2DM 中神经炎症发展的有前途的方法。
