2015 Annual Meeting Canadian Society of Pharmacology and Therapeutics

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Canadian Society of Pharmacology and Therapeutics


Pharmacology and Therapeutics



Subclinical endotoxemia has been reported in HIV infected individuals and immune activation may be exacerbated in these patients due to immune dysregulation. As infection- induced inflammation can alter the expression of placental drug transporters, it is plausible that this may be potentiated in HIV pregnant women. Similar to humans the HIV -Tg develops immune disorders and AIDS associated conditions. Therefore, our objective was to examine the impact of low -dose endotoxin on the expression of placental drug transporters in HIV -Tg rats.


3 -5 month pregnant HIV -Tg rats or wild -type littermates (WT) were treated with low dose endotoxin (0.1 or 0.25 mg/kg) on GD18 (n=4 -8/group) and placentas harvested 18 hr later. Gene expression was measured us ing qRT -PCR and serum cytokine levels were measured using ELISA.


Following endotoxin administration, there was a dose- dependent increase in pro- inflammatory cytokine levels in both HIV -Tg and WT rats, but to a greater extent in HIV -Tg. Endotoxin administration decreased the expression of Abcb1a, Slco2b1 and Slco4a1 in a dose dependent manner in HIV -Tg but not WT rats. Changes in transporter expression significantly correlated to cytokine induction. Endotoxin was associated with higher expression of Abcg2 in HIV -Tg and WT but only reached significance in HIV -Tg. Abcc3 expression was increased in endotoxin- treated WT but not HIV - Tg. Endotoxin administration did not impose significant changes in the expression of Abcb1b, Abcc1, Abcc2 and Abcc4 in HIV -Tg and WT rats.


Our results indicate that the inflammatory response is augmented in HIV -Tg rats following low dose exposure to endotoxin. Immune activation is associated with significant changes in the expression of several drug transporters in the placenta of HIV -Tg rats. Overall, our data suggests that placental transfer of drugs may be altered in the HIV population due to subclinical endotoxemia and other co- existing infections.

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