title: Melatonin alleviates hyperthyroidism induced oxidative stress and neuronal cell death in hippocampus of aged female golden hamster, Mesocricetus auratus.
abstract: Oxidative stress is a well known phenomenon under hyperthyroid condition that induces various physiological and neural problems with a higher prevalence in females. We, therefore investigated the antioxidant potential of melatonin (Mel) on hyperthyroidism-induced oxidative stress and neuronal cell death in the hippocampus region of brain (cognition and memory centre) of aged female golden hamster, Mesocricetus auratus. Aged female hamsters were randomly divided into four experimental groups (n=7); group-I: control, group-II: Melatonin (5mgkg(-1)day(-1), i.p., for one week), group-III: Hyperthyroid (100μg kg(-1)day(-1), i.p., for two weeks) and group-IV- Hyper+Mel. Hormonal profiles (thyroid and melatonin), activity of antioxidant enzymes (SOD, CAT and GPX), lipid peroxidation level (TBARS) and the specific apoptotic markers (Bax/Bcl-2 ratio and Caspase-3) expression were evaluated. A significant increase in the profile of total thyroid hormone (tT3 and tT4) in hyperthyroidic group as compared to control while tT3 significantly decreased in melatonin treated hyperthyroidic group. However, Mel level significantly decreased in hyperthyroidic group but increased in melatonin treated hyperthyroidic group. Further, the number of immune-positive cells for thyroid hormone receptor-alpha (TR-α) decreased in the hippocampus of hyperthyroidic group and increased in melatonin treated hyperthyroidic group. Profiles of antioxidant enzymes showed a significant decrease in hyperthyroidic group with a simultaneous increase in lipid peroxidation (TBARS). Melatonin treatment to hyperthyroidic group lead to decreased TBARS level with a concomitant increase in antioxidant enzyme activity. Moreover, increased expression of Bax/Bcl-2 ratio and Caspase-3, in hyperthyroidic group had elevated neuronal cell death in hippocampal area and melatonin treatment reduced its expression in hyperthyroidic group. Our findings thus indicate that melatonin reduced the hyperthyroidism-induced oxidative stress and neuronal cell death in the hippocampus region of brain, suggesting a novel therapeutic approach of melatonin for management of cognition and memory function in females under hyperthyroid condition.
authors.affiliation: College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, United States of America.
authors.forename: Geeta
authors.initials: G
authors.lastname: Rao
authors.affiliation: Department of Zoology, Banaras Hindu University, Varanasi, UP 221005, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Verma
authors.affiliation: Department of Zoology, Banaras Hindu University, Varanasi, UP 221005, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Department of Zoology, Banaras Hindu University, Varanasi, UP 221005, India. Electronic address: chaldar2001@yahoo.com.
authors.forename: Chandana
authors.initials: C
authors.lastname: Haldar
authors.affiliation: Department of Endocrinology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP 221005, India.
authors.forename: Neeraj Kumar
authors.initials: NK
authors.lastname: Agrawal
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D006980:Hyperthyroidism / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects; D008550:Melatonin / Q000008:administration & dosage*; D008647:Mesocricetus; D009474:Neurons / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D053148:Caspase 3; D008550:Melatonin
keywords: Hippocampus; Hyperthyroidism; Melatonin; Neuronal cell death; Oxidative stress