The effects of cyclophosphamide, melatonin and carvedilol on neural tube and skeletal system of mice fetuses in prenatal period

• Published in: Annals of anatomy 2011-10, Vol.193 (5), p.459-465
• Main Authors: Khaksary Mahabady, M., Najafzadeh Varzi, H., Bakhtiari, E.
• Format: Article
• Language: English
• Subjects: Abnormalities, Drug-Induced - prevention & control; Animals; Antioxidants - pharmacology; Bone Development - drug effects; Carbazoles - pharmacology; Carvedilol; Cyclophosphamide; Cyclophosphamide - pharmacology; Embryo malformations; Female; Fetus - abnormalities; Fetus - drug effects; Male; Melatonin; Melatonin - pharmacology; Mice; Mutagens - pharmacology; Neural Tube - abnormalities; Neural Tube - drug effects; Pregnancy; Propanolamines - pharmacology; Spine - abnormalities; Spine - drug effects; Teratogenicity
• ISSN: 0940-9602; 1618-0402
• DOI: 10.1016/j.aanat.2011.05.003

Cyclophosphamide (CP) as an alkylating agent is used for treatment of cancer and to prevent rejection of tissue transplantation. There are many reports that the teratogenic effects of cyclophosphamide can be prevented by application of antioxidant drugs and stimulation of the maternal immune system. Also, there is some evidence that melatonin and carvedilol are antioxidant.Therefore, in this study, the prophylactic effects of melatonin and carvedilol on teratogenic effects of CP was compared. This study was performed on 31 pregnant mice that were divided into six groups. The control group received normal saline and test groups received CP (20 mg/kg), carvedilol (5 mg/kg), melatonin (10 mg/kg), CP (20 mg/kg) pluscarvedilol (5 mg/kg) and CP (20 mg/kg) plus melatonin (10 mg/kg) intraperitoneally on the 10th day of gestation, respectively. Fetuses were collected on the 19th day of gestation and after determination of weight and length; they were stained by Alizarin red–Alcian blue method. Cleft palate, spina bifida and exencephalyincidence were 62.79%, 62.79% and 30.23% in fetuses of mice that received only CP. Cleft palate,spina bifida, exencephaly, and incidence were 45.45%, 9.09% and 0% in group which received CP plus carvedilol (5 mg/kg), respectively.However, cleft palate, spina bifida and exencephalyincidence were 62.5%, 45.83% and 4.16% range in the group which received CP plus melatonin (10 mg/kg), respectively. In addition, theincidence of skeletal anomalies including limb, vertebral, and sternaldefects were decreased by melatonin and carvedilol. The mean weight and length of animal fetuses that had received melatonin and carvedilol were significantly greater than those receiving only CP. It is concluded; carvedilol has a significant effect in preventing CP-induced malformations and in cases like CP-induced exencephaly, cleft palate and spina bifidahas better prophylactic effect than melatonin, but this improvement is not significant.