title: Evaluation of neuroprotection by melatonin against adverse effects of prenatal exposure to a nonsteroidal anti-inflammatory drug during peripheral nerve development.
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.
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Medipol University, Istanbul, Turkey.
authors.forename: Ilknur
authors.initials: I
authors.lastname: Keskin
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Ondokuz Mayis University, Samsun, Turkey. Electronic address: skaplan@omu.edu.tr.
authors.forename: Suleyman
authors.initials: S
authors.lastname: Kaplan
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Selcuk University, Konya, Turkey.
authors.forename: Serpil
authors.initials: S
authors.lastname: Kalkan
authors.affiliation: Department of Plastic Surgery, Medical Faculty, Medipol University, Istanbul, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Sutcu
authors.affiliation: Department of Histology and Embryology, Veterinary Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: M Basak
authors.initials: MB
authors.lastname: Ulkay
authors.affiliation: Department of Histology and Embryology, Veterinary Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: O Burak
authors.initials: OB
authors.lastname: Esener
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D004008:Diclofenac / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010525:Peripheral Nerves / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018696:Neuroprotective Agents; D004008:Diclofenac; D008550:Melatonin
keywords: Diclofenac sodium; Melatonin; Nerve; Neuroprotection; Prenatal exposure