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Evaluation of neuroprotection by melatonin against adverse effects of prenatal exposure to a nonsteroidal anti-inflammatory drug during peripheral nerve development
Institution:1. Department of Histology and Embryology, Medical Faculty, Medipol University, Istanbul, Turkey;2. Department of Histology and Embryology, Medical Faculty, Ondokuz Mayis University, Samsun, Turkey;3. Department of Histology and Embryology, Medical Faculty, Selcuk University, Konya, Turkey;4. Department of Plastic Surgery, Medical Faculty, Medipol University, Istanbul, Turkey;5. Department of Histology and Embryology, Veterinary Faculty, Istanbul University, Istanbul, Turkey;1. Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China;2. Department of Emergency, Yancheng Clinical Institute, Xuzhou Medical University (Yancheng City No.1 People''s Hospital), Yancheng, JiangSu Province, China;3. Department of Neurology, Yancheng Clinical Institute, Xuzhou Medical University (Yancheng City No.1 People''s Hospital), Yancheng, JiangSu Province, China;4. Neurosurgery Department, Shanghai Clinical Center of Chinese Academy of Sciences, Shanghai, China;1. California State University Northridge, Biology Deptartment, MC 8303. 18111 Nordhoff Street. Northridge, CA 91330, USA;2. Department of Neuroscience, Thomas Jefferson University, BLSB 306, Philadelphia, PA 19107, USA;1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, #108 Pyung-Dong, Jongno-Gu, Seoul, Republic of Korea;2. Division of Endocrinology and Metabolism, Department of Internal Medicine, Gangdong Kyunghee Hospital, Kyunghee University College of Medicine, #892 Dongnam-Ro, Gangdong-Gu, Seoul, Republic of Korea;3. Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul Saint Mary''s Hospital, The Catholic University of Korea College of Medicine, #222 Banpodae-Ro, Seocho-Gu, Seoul, Republic of Korea;4. Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, #148 Gurodong-Ro, Guro-Gu, Seoul, Republic of Korea;5. Division of Endocrinology and Metabolism, Department of Internal Medicine, Pyungchon Sacred Heart Hospital, Hallym University College of Medicine, #896 Pyungchon-Dong, Dongan-Gu, Anyang, Gyunggi-Do, Republic of Korea;6. Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Seoul Hospital, University of Sungkyunkwan College of Medicine, #50 Ilwon-Dong, Gangnam-Gu, Seoul, Republic of Korea;7. Division of Endocrinology and Metabolism, Department of Internal Medicine, Gil Hospital, Gacheon University College of Medicine, #774-2 Namdongdae-Ro, Namdong-Gu, Incheon, Republic of Korea;8. Division of Endocrinology and Metabolism, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, #50 Yonsei-Ro, Seodaemun-Gu, Seoul, Republic of Korea;9. Division of Endocrinology and Metabolism, Department of Internal Medicine, Bucheon Soonchunhyang Hospital, Soonchunhyang University School of Medicine, #170 Jomaru-Ro, Wonmi-Gu, Bucheon, Gyunggi-Do, Republic of Korea;10. Division of Endocrinology and Metabolism, Department of Internal Medicine, Boramae Hospital, Seoul National University College of Medicine, #20 Boramae-Ro5, Dongjak-Gu, Seoul, Republic of Korea;11. Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul Asan Hospital, Ulsan University, College of Medicine, #88 Olympic-Ro43, Songpa-Gu, Seoul, Republic of Korea
Abstract:The potential ability of melatonin to protect against impairment of the fetal peripheral nerve system due to maternal consumption of diclofenac sodium (DS) was investigated. Eighty-four pregnant rats were divided into seven groups: control (CONT), saline administered (PS), DS administered (DS), DS with low-dose melatonin administered (DS + MLT10), DS with high-dose melatonin administered (DS + MLT50), low-dose melatonin administered (MLT10), and high-dose melatonin administered (MLT50). After the pregnancy, six male newborn rats from each group were sacrificed at 4 and 20 weeks of age. Their right sciatic nerves were harvested, and nerve fibers were evaluated using stereological techniques. Mean numbers of myelinated axons, axon cross-section areas and the mean thickness of the myelin sheet were estimated. Four-week-old prenatally DS-exposed rats had significantly fewer axons, a smaller myelinated axonal area, and a thinner myelin sheath compared to CONT group (p < 0.05). Although melatonin at both doses significantly increased axon numbers, only a high dose of melatonin increased the diameter of those axons (p < 0.05). At 20-weeks of age, myelinated axon number in the DS group was not only significantly lower than all other groups (p < 0.05) but also the cross-sectional area of these axons was smaller than all other groups (p < 0.05). There were no differences between the groups regarding the mean thickness of the myelin sheet. The current study indicates that prenatal exposure to DS decreases the number and the diameter of sciatic nerve axons and that melatonin prophylaxis can prevent these effects.
Keywords:Nerve  Melatonin  Diclofenac sodium  Neuroprotection  Prenatal exposure
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