Neuroprotective Effects of Melatonin Against Neurotoxicity Induced by Intrahippocampal Injection of Aluminum in Male Wistar Rats: Possible Involvement of Oxidative Stress Pathway

Abstract

Aluminum (Al) is a well-established neurotoxicant, affecting various regions of the brain and causing many neuropathological and neurobehavioral abnormalities as well as oxidative stress (OS). Conversely, melatonin (MEL) has been considered as an antidepressant, anxiolytic substance and protects neurons from OS. The present study was designed to evaluate the neuroprotection effect of MEL against Al neurotoxicity and OS in male Wistar rats. Rats received an intraperitoneal and/or a single intrahippocampal injection of NaCl, MEL or AlCl 3 . Before two weeks of intrahippocampal surgery period, MEL (4 mg/kg) was intraperitoneally injected (Group II and Group IV). Thereafter, control group (group I) received 2 l NaCl (0.9%) and groups III and IV received 2 l AlCl 3 (2 mg/kg) intracerebrally into the right ventral hippocampus. Five days after treatment period, all the rats were subjected to the neurobehavioral tests. The animals were then decapitated and the hippocampus was removed. Biochemical parameters of OS and the histology of Cornu Ammonis 3 (CA3) area of the hippocampus were evaluated. The results clearly showed that Al induced anxiety and depressive-like behaviour and cognitive impairment. In the hippocampus, Al also increased the levels of lipid peroxidation (LPO) and nitric oxide (NO) and reduced the activity of superoxide dismutase (SOD) as well mediates brain damage in CA3 hippocampal area. These alterations were reversed by MEL. It can be concluded that, by exerting its properties against the oxidative action of this metal in the hippocampus, MEL may play a potential role in protecting against the behavioral and histopathological alterations induced by Al.