Histological and Morphometric Study on the Effects of Excess Retinoic Acid on Prenatal Liver Development in Albino Rats and the Potential Protective Role of Folic Acid.

Background: With appearance of excess use of vitamins and multivitamin regimens, Retinoic acid (RA) is a metabolite of vitamin A that is fundamental for cell growth and differentiation.Aim of the Work: To examine the impact of excess retinoic acid on the prenatal liver development of albino rats and explore the potential mitigating role of folic acid supplementation.Materials and Methods: Thirty adult pregnant female rats were divided into three groups. Control group (I), retinoic acid treated group (II) was given retinoic acid at a dose 50 mg/kg B.W./day, RA was dissolved in 0.1 ml of olive oil orally and the folic acid group (III) received retinoic acid following the same regimen as the experimental group (II), in addition to a 4.0 mg/kg dose of folic acid via intraperitoneal injection, starting on the first day of pregnancy and continuing until the day of sacrifice. On the 14th and 18th days of pregnancy, the mothers were euthanized, and the fetal livers were extracted, weighed, and prepared for histological examination. The removed liver was prepared for microscopic examination (light and electron). Additionally, morphometric analysis was conducted.Results: the control group exhibited normal histological structures, while the retinoic acid-treated group showed structural disruption of the hepatocytes. Added to that, wide congested hepatic blood vessels were observed. Vacuolation of hepatocytes with the appearance of large number of fat cell. Hepatic fibrosis was also detected. The morphometric analysis exhibited a notable reduction in the number of hepatocytes. conversely, rats taken folic acid with retinoic acid showed large improvement in hepatic architecture.Conclusion: Administering RA during embryonic growth caused harmful effects on the growing liver; so, treatment with RA should avoided at any stage of pregnancy. Also, taking folic acid early in pregnancy showed protective effect against many of these harmful effects.