Abstract
BACKGROUND AND PURPOSE: 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). EXPERIMENTAL APPROACH: 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 viz. 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. CONCLUSION AND IMPLICATIONS: Daily intake of MLN attenuates the exacerbation of cerebral ischemic injury in a diabetic state.