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

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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.

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Acknowledgments

Authors are thankful to the Department of Ayurveda, Yoga and Naturalpathy, Unani, Siddha and Homeopath (AYUSH), Ministry of Health and Family Welfare, Government of India, New Delhi for financial assistance. The authors wish to thank Mr. Dharamvir Singh for his assistance.

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Authors and Affiliations

  1. Department of Internal Medicine, Carver College of Medicine, 500 Newton Road University of Iowa, Iowa city, IA, 52242, USA

    Mohd. Moshahid Khan

  2. Brain Research Laboratory, Department of Emergency Medicine, Emory University, Atlanta, GA, 30322, USA

    Tauheed Ishrat

  3. Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA, 30912, USA

    M. Badruzzaman Khan

  4. Neurotoxicology laboratory, Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, 110062, India

    Ajmal Ahmad, Gulrana Khuwaja, Syed Shadab Raza, Pallavi Shrivastava & Fakhrul Islam

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  1. Ajmal Ahmad
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Correspondence to Fakhrul Islam.

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Ahmad, A., Khan, M.M., Ishrat, T. et al. Synergistic Effect of Selenium and Melatonin on Neuroprotection in Cerebral Ischemia in Rats. Biol Trace Elem Res 139, 81–96 (2011). https://doi.org/10.1007/s12011-010-8643-z

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  • DOI: https://doi.org/10.1007/s12011-010-8643-z

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