Long-term melatonin or 17beta-estradiol supplementation alleviates oxidative stress in ovariectomized adult rats.
Melatonin is an endogenously generated potent antioxidant. Our previous results indicated that melatonin improved learning and memory deficits in the transgenic mouse model of Alzheimer's disease (AD) and ovariectomized (OVX) rats by improving cholinergic nerve system dysfunction, preventing apoptosis. In this study we aim to investigate the antioxidative effects of melatonin or estradiol in the brains of ovariectomized rats. OVX Sprague-Dawley rats received daily injections of melatonin (5, 10, or 20 mg/kg), 17beta-estradiol (80 microg/kg), or sesame oil for 16 weeks. We found an increase in brain mitochondrial thiobarbituric acid-reactive substances (TBARS) levels, a decrease in mitochondrial glutathione (GSH) content as well as mitochondrial superoxide dismutase (SOD) activity and upregulation of the apoptotic-related factors, such as Bax, Caspase-3, and Prostate apoptosis response-4 (Par-4) in the frontal cortex of OVX rats. In addition to oxidative stress, OVX also caused decreased activities of mitochondrial respiration complex I and complex IV, which implicated mitochondrial dysfunction. Melatonin or 17beta-estradiol antagonized the detrimental effects induced by OVX. Furthermore, immunohistochemistry results revealed that the abnormal upregulation of the apoptotic related factor such as Bax, Caspase-3, and (Par-4) greatly reduced expression after melatonin or 17beta-estradiol supplement action. These findings demonstrate the important effects of melatonin or 17beta-estradiol on postmenopausal neuropathy and support the potential application of melatonin in the treatment of dementia in postmenopausal women. Early, long-term melatonin application is a promising strategy which could potentially be applied in a clinical setting.
Feng
Zheng
Z
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, No.1 Xiannong Tan Street, Beijing 10050, People's Republic of China.
Zhang
Jun-tian
JT
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins; D001921:Brain / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D019587:Dietary Supplements; D004579:Electron Transport; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D015227:Lipid Peroxidation; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D010053:Ovary / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017392:Thiobarbituric Acid Reactive Substances; C101296:prostate apoptosis response-4 protein; D004958:Estradiol; D013482:Superoxide Dismutase; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione; D008550:Melatonin