Avaliação de biomarcadores reprodutivos, bioquímicos e imunológicos em ratas Wistar imunossuprimidas pelo micofenolato de sódio, antes e durante a prenhez

Abstract

The use of medication during pregnancy should be taken with caution, especially because of its implications for maternal and fetal health. The mycophenolate sodium (MMS) is used to avoid possible rejection of transplanted tissues and organs by inhibiting T and B lymphocyte proliferation. Objective of this study was to evaluate the effects of maternal immunosuppression by MMS on reproductive, biochemical and immunological profile in rats. The rats were divided into three groups: rats treated with water (CONT = 10) rats orally treated with MMS (20mg/Kg) daily for 15 days until a positive diagnosis of pregnancy (MICO-1 = 10) and rats orally treated with MMS (20mg/Kg) daily for 15 days prior to and during 21 days of pregnancy (MICO-2 = 10). It was evaluated body weight, blood glucose, and water and food intake weekly (before and during pregnancy). On the 17th day of pregnancy it was performed the Oral Tolerance Glucose Test (OGTT) and on day 21 the rats were anesthetized and killed by decapitation and thus measured the relative maternal organs, determinations of reproductive parameters (Index fertility, childbirth, pregnancy and number of live births and resorption), serum biomarkers (lipid parameters and liver transaminases) and immunological profile (placental and serum TNF) in all groups. Statistical significance was p <0.05. In the pre-pregnancy period, although there were no changes in body weight values, the continuous treatment with MMS decreased food and water consumption and also increased blood glucose (MICO-2). During pregnancy period, these rats presented a reduction of the body weight, maintaining a mild hyperglycemia level (about 170 mg/dL) with normal OGTT. Furthermore, in the same study group showed other negative effects, including dead rats, total resorption of fetuses increased relative weight of liver, spleen (including leukocytes rate) and also periovarian fat. Moreover, it reduced rates serum lipid (cholesterol and lipoprotein fractions, triglycerides and alanine aminotransferase). The continued use of MMS during pregnancy can be considered toxic, damaging the maternal and fetal health, lead to hyperglycemia, fetal loss and splenic dysfunction interfering with lipid metabolism and immune profile. This study shows that MMS use is not recommended during pregnancy freely and should be replaced by another immunosuppressant.