Synergistic Effect of Selenium and Melatonin on Neuroprotection in Cerebral Ischemia in Rats

Abstract

The synergistic scavenger effects of selenium and melatonin collectively we called Se-Mel was studied on the prevention of neuronal injury induced by ischemia/reperfusion. Male Wistar rats were treated with sodium selenite (0.1 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) 30 min before the middle carotid artery occlusion (MCAO) and immediately after MCAO to male Wistar rats and was continued for 3 days once daily at the interval of 24 h. Behavioral activity (spontaneous motor activity and motor deficit) was improved in Se-Mel-treated rats as compared to MCAO group rats. The level of glutathione and the activity of antioxidant enzymes was depleted significantly while the content of thiobarbituric acid reactive substances, protein carbonyl, and nitric oxide radical (NO(·)) was increased significantly in MCAO group. Systemic administration of Se-Mel ameliorated oxidative stress and improves ischemia/reperfusion-induced focal cerebral ischemia. Se-Mel also inhibited inducible nitric oxide synthase expression in Se-Mel+MCAO group as compared to MCAO group rats. Thus, Se-Mel has shown an excellent neuroprotective effect against ischemia/reperfusion injury through an anti-ischemic pathway. In conclusion, we demonstrated that the pretreatment with Se-Mel at the onset of reperfusion, reduced post-ischemic damage, and improved neurological outcome following transient focal cerebral ischemia in male Wistar rat.

Effects of Selenium on Axon and Myelin Healing in an Experimental Sciatic Nerve Injury Model

“…It has been shown that selenium plays an important role in the continuation of the physiological functions of the nervous system (such as signal transduction and development) (10). Previous studies have shown that selenium has a neuroprotective role in various experimental pathologies, such as spinal cord injury, cerebral ischemia and neurotoxicity models (11)(12)(13)(14)(15). Similarly, in our previous study, selenium prevented neurotoxicity that was induced by cisplatin in a partial level (16).…”

“…Previous studies conducted with neurotoxic agents have demonstrated the neuroprotective effect of selenium on the central and peripheral nervous systems (8,(13)(14)(15)(16). However, this study was the first to demonstrate that selenium has a neuroprotective effect on peripheral nerve injury in rats.…”

Effect of Sodium Selenite on Lipid Peroxidation and Glutathione in Alloxan Induced Diabetic Rats

“…Previous studies showed that using natural antioxidants supplements such as vitamin E (32), α-lipoic acid (33), flavonoids (34), oleanolic acid (35), selenium (36), vanadium, α-carotene, zinc, vitamin C (37, 38), aminoguanidine (39), lycopene (40) and natural phenolic compounds have protective effects on lipid peroxidation in diabetics and chronic disease (41). Several reports showed that selenium has neuroprotective effect and in cerebral ischemia and improves antioxidant capacity in vitro and in vivo in patients with coronary artery disease (42,43). The protective role of selenium administration against oxidized low density lipoprotein and antioxidant defense in diabetic rats was reported (44).…”

Selenium in the therapy of neurological diseases. Where is it going?

“…The human brain is characterised by a low (2,3%) content of Se [5]; however, it shows high priority for Se uptake in the case of its dietary deficiency. Even markedly decreased levels of Se in blood as observed in young rats on an Se-deficient 13-week diet, did not induce the significant changes in Se concentration in the brain [25].…”

“…Se is mainly consumed via food, which is a major source of organic Se at oxidation state II, which is better absorbed than the inorganic forms that are present in water. The total amount of Se in adult humans varies from between 10 to 20 mg and depends on many factors, such as place of living or health [3,5].…”