Saleh Dalia O, Jaleel Gehad A Abdel, Al-Awdan Sally W, Hassan Azza, Asaad Gihan F
Pharmacology Department, National Research Centre, Dokki, Giza, Egypt.
Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
Res Pharm Sci. 2020 Oct 19;15(5):418-428. doi: 10.4103/1735-5362.297844. eCollection 2020 Oct.
Diabetes mellitus is a disorder accompanied by oxidative and inflammatory responses, that might exacerbate vascular complications. The purpose of this study was to investigate the potential antioxidant and anti-inflammatory effects of melatonin (MLN) on streptozotocin (STZ)-induced diabetic rats subjected to middle cerebral artery occlusion followed by reperfusion (MCAO/Re).
Diabetes was induced in rats by a single injection of STZ (55 mg/kg; i.p.). The cerebral injury was then induced by MCAO/Re after six weeks. After 24 h of MCAO/Re the MLN (10 mg/kg) was administered orally for 14 days. Serum and tissue samples were extracted to determine malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), interleukin-1β (IL-1β), and the tumor necrosis factor- α (TNF-α). Part of the brain tissue was kept in formalin for pathological and immunohistochemical studies to determine nuclear factor kappa B (NF-kB) and cyclooxygenase-2 (COX-2) immune reactivity.
FINDINGS/RESULTS: MCAO/Re in STZ-induced hyperglycaemic rats caused a decrease in brain GSH, an increase in brain MDA, and NO was increased in both serum and brain tissue. Rats showed a prominent increase in the serum and brain inflammatory markers . IL-1β and TNF-α. Oral treatment with MLN (10 mg/kg) for two weeks reduced the brain levels of MDA, NO, IL-1β, and TNF-α. Impressive amelioration in pathological findings, as well as a significant decrease in NF-kB and COX2 immune stained cells of the cerebral cortex, hippocampus, and cerebellum, occurred after treatment with MLN. It also succeeded to suppress the exacerbation of damage in the brain of hyperglycaemic rats.
Daily intake of MLN attenuates the exacerbation of cerebral ischemic injury in a diabetic state.
糖尿病是一种伴有氧化和炎症反应的疾病，可能会加剧血管并发症。本研究的目的是探讨褪黑素（MLN）对链脲佐菌素（STZ）诱导的糖尿病大鼠大脑中动脉闭塞再灌注（MCAO/Re）后的潜在抗氧化和抗炎作用。
通过单次腹腔注射STZ（55mg/kg）诱导大鼠患糖尿病。六周后通过MCAO/Re诱导脑损伤。MCAO/Re 24小时后，口服MLN（10mg/kg），持续14天。提取血清和组织样本以测定丙二醛（MDA）、还原型谷胱甘肽（GSH）、一氧化氮（NO）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）。将部分脑组织保存在福尔马林中用于病理和免疫组织化学研究，以确定核因子κB（NF-kB）和环氧化酶-2（COX-2）的免疫反应性。
STZ诱导的高血糖大鼠MCAO/Re导致脑GSH降低、脑MDA增加，血清和脑组织中的NO均升高。大鼠血清和脑炎症标志物IL-1β和TNF-α显著增加。口服MLN（10mg/kg）两周可降低脑MDA、NO、IL-1β和TNF-α水平。MLN治疗后，病理结果有显著改善，大脑皮质、海马和小脑的NF-kB和COX2免疫染色细胞显著减少。它还成功抑制了高血糖大鼠脑损伤的加剧。
每日摄入MLN可减轻糖尿病状态下脑缺血损伤的加剧。
