The protective effect of exogen melatonin upon fetal hippocampus damage caused by high-dose caffeine administration in pregnant rats

Abstract

Abstract Objective: Caffeine (CAF), which is in the methylxanthines group (1,3,7-trimethylxanthine), is a neurologically active food component that is widely consumed and has a stimulating effect on the central nervous system. CAF taken in high doses during pregnancy rapidly crosses the placenta and causes many negative conditions such as low birth weight infants, premature births, spontaneous abortion, stillbirth, and principally fetal growth retardation. On the other hand, melatonin (MEL) is an endogenous hormone secreted from the pineal gland that plays a role in the regulation of many biological functions such as sleep, biological rhythm, reproduction, immunity and has neuroprotective effects. In this study, we aimed to investigate the possible effects of exogenous MEL on the fetal hippocampus damage caused by high-dose CAF administration in pregnant rats. Methods: In the study, 32 adult Wistar albino female rats were divided into four experimental groups after conception (n=8). No compound was administered to the control group. In the MEL group, intraperitoneal (i.p.) MEL was administered at a dose of 10 mg/kg/day at 9-20 days of pregnancy. In the CAF group, i.p. CAF was administered at a dose of 60 mg/kg/day at 9-20 days of pregnancy. In the CAF plus MEL group, i.p. CAF and MEL were administered at a dose of 60 mg/kg/day and 10 mg/kg/day, respectively at 9-20 days of pregnancy. Histological tissue processing procedures were performed after the extraction of the brains of the fetuses sacrificed on the 21st day of pregnancy. Hippocampal regions of fetal brains were analyzed by Hematoxylin and Eosin (H&E) and Cresyl Echt Violet (CEV) histochemical staining, anti-GFAP and anti-synaptophysin immunohistochemical staining methods. Results: While there was a decrease in fetal and brain weights in the CAF group, it was found that the CAF plus MEL group had a closer weight average to that of the control group. In histological examinations, while the MEL group showed similar characteristics with the control group, it was observed that the pyramidal cell layer consisted of 8-10 layers of cells due to the delay in migration in hippocampal neurons in the CAF group. It was found that these findings decreased in the CAF plus MEL group. Conclusion: Ultimately, it was determined that high-dose CAF administration caused delays and deterioration in neurogenesis in the fetal hippocampus region, and it was also shown that MEL administration was effective in reducing these findings.