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

Autor: Adham M. Maher, Galila A. Yacout, Samar R. Saleh, Hagar M. Hashem, Nihal M. Elguindy
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Anti-Inflammatory Agents
Nitric Oxide Synthase Type II
medicine.disease_cause
Systemic inflammation
Hippocampus
030226 pharmacology & pharmacy
Antioxidants
Rats
Sprague-Dawley
chemistry.chemical_compound
0302 clinical medicine
Malondialdehyde
General Pharmacology
Toxicology and Pharmaceutics
Melatonin
biology
Leptin
General Medicine
Glutathione
Nitric oxide synthase
Acetylcholinesterase
Cytokines
medicine.symptom
hormones
hormone substitutes
and hormone antagonists
Signal Transduction
medicine.drug
medicine.medical_specialty
Diet
High-Fat
General Biochemistry
Genetics and Molecular Biology
Diabetes Mellitus
Experimental
03 medical and health sciences
Internal medicine
medicine
Animals
Indoleamine-Pyrrole 2
3
-Dioxygenase
Neuroinflammation
Inflammation
business.industry
nutritional and metabolic diseases
Rats
Oxidative Stress
030104 developmental biology
Endocrinology
Diabetes Mellitus
Type 2
chemistry
biology.protein
Nervous System Diseases
business
Oxidative stress
Zdroj: Life Sciences. 247:117427
ISSN: 0024-3205
Popis: Aim of the work 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. Main methods 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. Key findings 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. Significance 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.
Databáze: OpenAIRE
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