Dysregulation of renal transporters in a rodent model of viral Infection.

Inflammation elicited by viral mimetic poly I:C has been shown to impose changes in the expression of drug transporters in the placenta and maternal liver in rats at term pregnancy. This was associated with altered drug disposition in the mother and fetus. Renal transporters play an important role in the elimination of several drugs taken by pregnant women. We examined the impact of poly I:C on the expression of renal transporters in pregnant rats at term. Pregnant Sprague-Dawley rats received single intraperitoneal dose of either poly I:C (5 mg/kg) or saline at gestation day 18 (n = 8/group). Animals were euthanized 24 h after the injection. The mRNA and protein expression of pro-inflammatory cytokines and transporters were measured by qRT-PCR and western blot. Poly I:C caused a fourfold increase in the mRNA of IL-6 in the kidney. As compared to saline controls, the mRNA expression of Mrp2, Bcrp, Octn1, Oat1, Oat2, Oat3, Urat1, Oatp4c1, and Pept2 was downregulated, whereas the Ent1 mRNA was increased. Protein expression of Bcrp, Urat1 and Pept2 were significantly decreased. While there was a trend towards reduced Mrp2, Oat2 and Oat3 protein expression, this did not reach significance. Poly I:C did not impact mRNA levels of Mdr1a, Mdr1b, Mrp4, Oct1, Oct2, Oct3, Octn2, Mate1, Ent2 or Pept1. Viral-induced inflammation mediates significant changes in the expression of several key drug transporters in the kidney of pregnant rats. Many clinically important drugs are substrates for these transporters. Therefore, inflammation-mediated alterations in transporter expression could affect their maternal and fetal disposition.