The Effect of Maternal Low Protein Diet on Rat Renal Organic Anion Transporter 1

It has been demonstrated that subjects with low birth weight (LBW) are at a greater risk for the onset of adult pathologies such as diabetes mellitus, hypertension, hyperlipidemia, high blood pressure, and obesity. From a pharmacological perspective, these pathologies necessitate intense drug therapies. Organs involved in the absorption, distribution, metabolism and/or elimination of drugs are shown to be structurally and morphologically altered in LBW animals. A decrease in kidney size makes the study of renal drug transporters important for predicting LBW induced adverse drug reactions and/or altered drug therapy. The purpose of this study is to evaluate the effect of LBW on the expression of Organic Anion Transporter-1 (OAT1) at the mRNA and protein level(s) in juvenile (day28 old), adolescent (day65 old), and adult (day150 old) rats. Protein restriction (maternal low protein diet) is one common animal model used to induce and study LBW, and it is the model employed in this study. Using RT-PCR, it was shown that mRNA levels were significantly decreased in the LBW adult offspring, in a sex dependent manner. Western blotting of various membrane fractions indicated further disregulation at the protein level. In conclusion, there are interesting differences in the transcriptional and translational regulation of OAT1 in the LBW animals. Further studies could lead to more clinically relevant implications of this data, as well as a more mechanistic understanding of the changes in OAT1 in this model