PMID- 15964511 OWN - NLM STAT- MEDLINE DCOM- 20051024 LR - 20131121 IS - 0891-5849 (Print) IS - 0891-5849 (Linking) VI - 39 IP - 2 DP - 2005 Jul 15 TI - Long-term melatonin or 17beta-estradiol supplementation alleviates oxidative stress in ovariectomized adult rats. PG - 195-204 AB - 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. FAU - Feng, Zheng AU - Feng Z AD - 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. FAU - Zhang, Jun-tian AU - Zhang JT LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050325 PL - United States TA - Free Radic Biol Med JT - Free radical biology & medicine JID - 8709159 RN - 0 (Antioxidants) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Thiobarbituric Acid Reactive Substances) RN - 0 (prostate apoptosis response-4 protein) RN - 4TI98Z838E (Estradiol) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 3.4.22.- (Casp3 protein, mouse) RN - EC 3.4.22.- (Casp3 protein, rat) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspases) RN - GAN16C9B8O (Glutathione) RN - JL5DK93RCL (Melatonin) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Apoptosis Regulatory Proteins MH - Brain/metabolism MH - Caspase 3 MH - Caspases/metabolism MH - Dietary Supplements MH - Electron Transport MH - Estradiol/*pharmacology MH - Female MH - Glutathione/metabolism MH - Immunohistochemistry MH - Intracellular Signaling Peptides and Proteins/metabolism MH - Lipid Peroxidation MH - Melatonin/metabolism/*pharmacology MH - Mitochondria/metabolism MH - Ovary/pathology MH - Oxidative Stress/*drug effects MH - Rats MH - Rats, Sprague-Dawley MH - Superoxide Dismutase/metabolism MH - Thiobarbituric Acid Reactive Substances/metabolism MH - Time Factors MH - Up-Regulation EDAT- 2005/06/21 09:00 MHDA- 2005/10/26 09:00 CRDT- 2005/06/21 09:00 PHST- 2004/12/14 00:00 [received] PHST- 2005/02/25 00:00 [revised] PHST- 2005/03/07 00:00 [accepted] PHST- 2005/06/21 09:00 [pubmed] PHST- 2005/10/26 09:00 [medline] PHST- 2005/06/21 09:00 [entrez] AID - S0891-5849(05)00133-4 [pii] AID - 10.1016/j.freeradbiomed.2005.03.007 [doi] PST - ppublish SO - Free Radic Biol Med. 2005 Jul 15;39(2):195-204. doi: 10.1016/j.freeradbiomed.2005.03.007. Epub 2005 Mar 25.