دراسة تأثير دواء Levetiracetam على عملية انغراس الاجنة وعلى بعض انسجة الجرذان الحوامل واجنتها

Studying the effect of Levetiracetam on the embryo implantation process and on some tissues of pregnant rats and their fetuses

The current study aimed to reveal some of the potential effects of the drug Levetiracetam at two concentrations (100, 200) mg/kg of body weight on the embryo implantation process and histological changes in the ovaries, liver, and kidneys of pregnant rats during the 7th day of pregnancy. And the body weights and lengths of the fetuses and the liver and kidney tissue of the pregnant rats and their fetuses on the 18th pregnancy day. The current study was conducted between 10/10/2022 and 7/5/2023 in the animal house of the College of Pharmacy / University of Karbala.
The study included 52 white rats, including 10 fertile male rats, whose ages ranged from more than nine weeks, and their weights ranged between (160-220) grams. They were used for insemination only, while the number of female rats was (42) whose ages ranged between (9-11). A week, its weight is between (160-220) grams. Pregnant female rats were divided into three main groups, each including (14) pregnant rats. The first group was dosed orally with physiological saline solution (NaCl 0.9%) throughout the pregnancy and was considered a control group. In contrast, the second group was dosed with levetiracetam (Lev) at 100 mg/kg body weight. The third group was dosed with levetiracetam (Lev), a concentration of 200 mg/kg of body weight daily from the beginning of pregnancy until the end of the experiment.
Each main group was divided into two subgroups, including 7 pregnant females. The pregnant rats in all groups were dosed from the first day of pregnancy until the end of the experiment with a single daily dose orally. The first subgroup of each main group was sacrificed during the 7th day of pregnancy, while the second subgroup was sacrificed during the 18th pregnancy day.
The results of the current study of histological sections of the uterine horns at the implantation sites showed that there were no abnormal or harmful effects of the implantation process on the embryos in the two groups treated with levetiracetam at two concentrations (100 and 200) mg/kg during the 7th day of pregnancy. The formation of deciduous tissue was normal in them compared to the control group for the same duration of pregnancy, that is, until the 7th day.
The results of the histological study of the ovaries of pregnant female rats for (7) days showed that there were no histological-pathological changes in them in the two groups that were dosed with levetiracetam at two concentrations (100, 200) mg/kg when compared with the histological structure of the ovaries of the control group for (7) days of Pregnancy. In contrast, histological sections of the livers and kidneys of pregnant females showed that they were treated with levetiracetam at two concentrations (100 and 200) mg/kg. Pathological effects on the liver tissue during the two days of pregnancy (7 and 18 days), which were represented by expansion of the central vein and destruction of its wall with congestion in it and expansion of the sinusoids, necrosis and degeneration of hepatic cells, infiltration of inflammatory cells, and irregularity of hepatic cells. While the kidneys of pregnant rats suffered from glomerular atrophy, expansion of Bowman’s space, infiltration of inflammatory cells, destruction of kidney tissue, degeneration of urinary tubule cells, destruction of the wall of Bowman’s capsule, with necrosis and destruction of cells in the urinary tubules, shedding of the tubules of the urinary tubules, and bleeding. Blood and congestion in the urinary tissue were compared with the liver and kidney tissue of pregnant rats in the control group for the exact two durations of pregnancy (7 and 18) days, respectively.
The livers and kidneys of fetuses of pregnant rats treated with levetiracetam at two different concentrations (100 and 200) mg/kg also showed negative histological changes caused by the drug during the gestation (day 18), such as atrophy in the glomerulus, irregularity and expansion of Bowman’s capsule, and destruction and necrosis of the walls of the urinary tubules (Proximal and distal), congestion of the glomerulus, and tissue degeneration. The liver of the fetuses showed bleeding in the tissue, expansion and congestion of the central vein, irregularity of the liver cells, and expansion of the sinusoids, compared with the histological structure of these organs in the fetuses of pregnant female rats of the control group and during 18th pregnancy day.
The results of the statistical analysis recorded a significant decrease (P < 0.05) in the weights and body lengths of the fetuses of pregnant female rats in the two groups that were treated with levetiracetam at two concentrations (100, 200) mg/kg during 18th pregnancy day compared with the control group and during 18th pregnancy day. The results also indicated significant differences (P < 0.05) in the weights and lengths of the fetuses between the two groups treated with the drug for both concentrations of 100 mg/kg and 200 mg/kg when comparing them.
It has been concluded from the current study that the drug Levetiracetam (LEV), at doses of 100 and 200 mg/kg, has harmful effects on some fetal and histological parameters of some organs during pregnancy (7 and 18 days), respectively.