Effect of Perinatal Low Protein Diet on the expression of P-Glycoprotein and Organic Cation Transporter Novel-Type-2 in the Heart

June 2012Many studies in recent literature have shown a significant link between the abnormalities of a newly born individual and the type of environment that their mothers encountered during pregnancy. More specifically, over the last two decades, a discipline of research commonly known as “fetal programming” has linked abnormalities at birth to quality of life during adulthood1. Low birth weight (LBW), a surrogate measure of adverse in utero environment, is strongly linked to high incidence of chronic diseases such as hypertension, diabetes, high cholesterol, and obesity later in life2.Previous and ongoing research in our laboratory has examined the effect of changes in kidney, liver, and brain, on the expression of drug metabolizing enzymes and transporters. Significant changes were reported in these organs that could adversely affect drug pharmacokinetics. \ud The expressions of mRNA for both P-gp and Octn2 in cardiac tissue were measured using RT-qPCR. Maternal control diet is given to produce control subjects after parturition, and the diet is kept for the pups until sacrificing on day 150. A maternal low protein diet is given to produce low-birth weight animal- model rat subjects after parturition, and the diet is kept for pups until the end of lactation when they are weaned. Then, low-birth weight animals are given control diet from end of lactation until day 150, when they are sacrificed.\ud The mRNA expression of P-gp is less abundant in low birth weight males than control ones by about two folds. On the other hand, there is an increased expression of P-gp in low birth weight females comparing to control group.Our focused research on cardiac drug transporter proteins suggests that the drug accumulation and pharmacotherapeutic outcomes could be determined partly by in utero conditions. Moreover, the gender specific alterations caution the generalization of above findings