Protective roles of nanomelatonin in cerebral ischemia-reperfusion of aged brain: Matrixmetalloproteinases as regulators

• Published in: Experimental gerontology 2017-06, Vol.92, p.13-22
• Main Authors: Sarkar, Sibani, Mukherjee, Abhishek, Das, Nirmalendu, Swarnakar, Snehasikta
• Format: Article
• Language: English
• Subjects: Aging - metabolism; Animals; Antioxidants - chemistry; Antioxidants - pharmacology; Blood-brain barrier; Blood-Brain Barrier - metabolism; Brain Ischemia - drug therapy; Cerebral ischemia-reperfusion; Disease Models, Animal; Female; Matrix metalloproteinase; Matrix Metalloproteinases - metabolism; Melatonin - chemistry; Melatonin - pharmacology; Mitochondria - drug effects; Mitochondria - metabolism; Nanocapsules - chemistry; Nanoencapsulated melatonin; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reperfusion Injury - drug therapy
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2017.03.009

Cerebral ischemia-reperfusion (CIR) injury occurs as a result of oxygen occlusion in the carotid artery through embolus or thrombus formation or cerebrovascular hemorrhage. The oxygen thrust during reperfusion causes the generation of reactive oxidative species (ROS) which exert a potential threat to neuronal survival. ROS may possibly be arrested by antioxidants. After CIR, extracellular matrix remodeling takes place, which is governed by matrix metalloproteinases (MMPs). Augmentation of lipid per oxidation, perturbation of antioxidant enzyme activities and the loss of pyramidal neuronal cells in rat brain were attributed to CIR injury. Melatonin can readily cross the blood-brain barrier (BBB) to exert protective effects as an antioxidant but it is quickly cleared by the circulating blood. Also melatonin is easily degraded by light and hence is found to be ineffective during daytime. Results of the present study showed that unlike free melatonin (FM), the application of nanocapsulated melatonin (NM) exhibited significantly higher potential even at much lower concentrations to rescue neuronal cells and mitochondria during CIR insult and also restored the activities of antioxidative enzymes and MMPs to their normal levels. Hence, nanoencapsulated melatonin may be considered as a suitable drug delivery system for brain to exert protection against CIR injury. •Polymeric nanocapsulated melatonin prepared and characterized.•Delivery via oral route to brain to confer protection against oxidative stress.•Counteracts oxidative damage by scavenging reactive oxygen species.•Inhibits oxidative stress induced neuronal apoptosis.•Promising formulation for treatment of oxidative stress induced neurodegeneration.