Investigation of the possible effects of melatonin upon fetal hippocampal damage produced by high dose caffeine administration in pregnant rats

Caffeine is a neurologically active food component that we all consume almost everyday and have a stimulating effect on the central nervous system. Caffeine in the methylxanthines group (1,3,7-trimethylxanthine) is the most commonly used psychoactive substance in the world. Unlike other psychoactive substances, caffeine is both common and legal. Caffeine and its derivatives are found in many consumed beverages and foods such as coffee, tea, cola and chocolate. The negative effects of caffeine on human health began to be investigated in the early 1900s. According to recent studies, more than 300 mg of caffeine is consumed on average per day. The normal daily dose range of caffeine is indicated as approximately 50-300 mg, allowing the person to be alert, energized and concentrated. In overdose consumption, ie 300-800 mg and above, it is stated that caffeine causes sleep disorder, irritability, anxiety and panic attacks. In daily usage 80 percent of women consumes caffeine during pregnancy and according to studies conducted on pregnant women caffeine had harmful effects on fetuses. It is stated that caffeine consumed especially during pregnancy has many negative effects on the fetus. The main reason for this is that the mother's caffeine can easily cross the placenta barrier. Cytochrome P450 A2, the enzyme required for caffeine metabolism, is absent in the placenta and fetus. Thus, the fetus, which lacks sufficient enzyme system, takes a long time to metabolize caffeine and therefore represents a risk factor for the fetus. Caffeine, taken in high doses during pregnancy, passes the placenta barrier rapidly and shows many negative conditions, mainly intra uterine growth retardation and also low birth weight infant, premature birth, spontaneous abortion and stillbirth. Melatonin is an endogenous hormone that plays a role in the regulation of many biological functions, including sleep, biological rhythm, reproduction and immunity, secreted from the gland called epiphysis cerebri or pineal gland. Numerous studies have shown that melatonin has a neuroprotective effect and increases nerve regeneration. Based on this information, we aimed to investigate the possible effect of melatonin on fetal hippocampal damage by high dose caffeine administration in pregnant rats. In our study, 32 adult "Wistar albino'' female rats were used. Female rats were randomly divided into 8 rats per group (n = 8); Female rats were divided into four groups as control, melatonin, caffeine and caffeine + melatonin, respectively. Female rats that were allowed to pregnancy were administered with substances according to their groups on the 9th day of pregnancy. No substance was administered to the control group. The melatonin group (MEL group) was administered at a dose of 10 mg/kg/day melatonin intraperitoneally (i.p.) between 4pm and 5pm and every day from 9th to 20th days of pregnancy. The caffeine group (CFN group) was administered at a dose of 60 mg/kg/day caffeine i.p every day from 9th to 20th days of pregnancy. The caffeine + melatonin group (CFN + MEL group) was administered at a dose of 60 mg/kg/day caffeine i.p every day from 9th to 20th days of pregnancy. In addition, CFN + MEL group was administered at a dose of 10 mg/kg/day melatonin i.p between 4pm and 5pm and every day from 9th to 20th days of pregnancy. All 32 Wistar albino pregnant rats included in this study and brain of the fetuses, which taken on the 21st day of pregnancy, were extracted. After fixation of hippocampal regions of the fetuses in all groups, hippocampal tissues stained with hematoxylin&eosin and cresyl echt violet for histochemical evaluation. In addition, immunohistochemical staining was performed with GFAP and synaptophysin. Keywords: Fetus, pregnant rat, hippocampus, caffeine, melatonin.