Toxic effects of glibenclamide in fetuses of normoglycemic rats: an alternative therapy for gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is defined as glucose intolerance first diagnosed during the second or third trimester of pregnancy. The treatment aims at glycemic control through changes in the patient s diet with or without exercise, but some patients need insulin therapy. An alternative would be to use oral hypoglycemic agents such as glibenclamide (GLIB). The present study aims to analyze the toxic effects of GLIB in fetuses of pregnant rats which received 5 or 20mg/kg doses of GLIB. Glycemic dosage reveals no significant difference between control (deionized water) and treated groups, showing that these concentrations of GLIB were not effective to cause hypoglycemia in rats. The vitality of the fetuses in all groups was 100%. GLIB administration promoted increase in weight and significant changes in measures of external morphological parameters of treated fetuses. Histological analysis revealed that liver lobes, lobules and central lobular veins were well defined for all treatments. However, GLIB animals presented a light brownish precipitate into the center-lobular veins and in the liver parenchyma among the hepatocytes. These results indicated a possible passage of the drug through the blood-placental membrane, without serious changes that impair the development of neither bone tissue, nor the liver of these animals.