Exogenous melatonin restrains neuroinflammation in high fat diet induced diabetic rats through attenuating indoleamine 2,3-dioxygenase 1 expression

• Published in: Life sciences (1973) Vol. 247; pp. 117427 - 11
• Main Authors: Maher, Adham M., Saleh, Samar R., Elguindy, Nihal M., Hashem, Hagar M., Yacout, Galila A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.04.2020; Elsevier BV
• Subjects: Acetylcholinesterase; Acetylcholinesterase - metabolism; Adiponectin; Animals; Anti-Inflammatory Agents - therapeutic use; Antioxidants; Antioxidants - pharmacology; Blood; Brain; Complications; Cytokines; Cytokines - metabolism; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2 - metabolism; Diet; Diet, High-Fat; Euthanasia; Glutathione; Glutathione - metabolism; High fat diet; Hippocampus; Hippocampus - metabolism; Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism; Inflammation; Inflammation - drug therapy; Interleukin 6; Leptin; Male; Malondialdehyde; Malondialdehyde - metabolism; Melatonin; Melatonin - therapeutic use; Morphology; Nervous System Diseases - drug therapy; Nitric oxide; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Oxidative stress; Oxidative Stress - drug effects; Rats; Rats, Sprague-Dawley; Rodents; Signal Transduction; Tryptophan 2,3-dioxygenase; Tumor necrosis factor-α; Type 2 diabetes mellitus; Melatonin; Triazole; Diethyl ether; Formalin; Inflammation; Type 2 diabetes mellitus; Sodium hydroxide; High-fat diet; Phosphate buffer saline; 3,5-dichloro-2-hydroxybenzenesulfonate; Potassium iodide; Sodium potassium tartrate; Hippocampus; Copper sulfate
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.117427

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. The ability of melatonin to resolve neuroinflammation provoked in a HFD- T2DM rat model through exerting its hypoglycemic effect by restoring pancreatic function, decreasing the adipose tissue mass and alleviating the state of dyslipidemia, all of which will lead to a systemic inflammation mitigation ultimately causing the extenuation of neuroinflammation through diminishing the oxidative stress in the brain and repressing the expression of iNOS, AChE and IDO1 key contributors to the hippocampal inflammation. [Display omitted]