Effect of Pethidine Hydrochloride on the Development of Neural Tube: A Genetic Analysis Study in a Chick Embryo Model

Abstract

Neural tube defects are among the most frequent congenital abnormalities of the central nervous system. Progression of neural tube deficits is affected by hereditary predilection and environmental determinants. Pethidine (meperidine) is a fast and powerful opioid analgesic in U.S. Food and Drug Administration category C. There are reports about developmental anomalies due to this medication. The aim of this study was to investigate the effects of different doses of pethidine hydrochloride on neural tube development in a chick embryo model resembling the first month of vertebral growth in mammals. Seventy-five specific pathogen-free eggs were incubated for 28 hours and divided into 5 groups (including the control group), each consisting of 15 eggs. Pethidine hydrochloride was administered sub-blastodermically with a Hamilton microinjector in 4 different doses. Incubation was continued until the end of the 48th hour. Subsequently, all eggs were opened, and embryos were cut from the embryonic membranes and evaluated morphologically, genetically, and histopathologically. Crown-rump length, somite numbers, and silver-stained nucleolar organizer region (AgNOR) number averages, and total AgNOR/nuclear area ratios decreased in a dose-dependent manner. Examination of neural tube closure revealed statistically significant differences in all experimental groups (P<0.05). Messenger RNA levels of the BRE gene were decreased in pethidine hydrochloride-exposed embryos compared with the control group. Although this downregulation was not statistically significant, this decrease was striking with a 0.422-fold change in the fifth group. We demonstrated that pethidine hydrochloride affects neuronal development in chicken embryos. The teratogenic mechanism of pethidine hydrochloride is unclear; therefore, further investigation is required.