Endotoxin Modulates the Expression of Renal Drug Transporters in HIV-1 Transgenic Rats

Journal of Pharmacy & Pharmaceutical Sciences : a Publication of the Canadian Society for Pharmaceutical Sciences, Société Canadienne Des Sciences Pharmaceutiques
Navaz Karimian Pour, Micheline Piquette-Miller

Abstract

Bacterial co-infections and low grade endotoxemia are common in HIV patients. Inflammation due to endotoxin or HIV may influence the expression and activity of transporters. Kidney transporters influence renal drug clearances including many antiretroviral agents. Our objective was to study the effect of endotoxin and HIV on the renal expression of drug transporters in an HIV-transgenic (HIV-Tg) rat model. These rats develop immune dysfunction and AIDS-associated conditions like humans. Endotoxin or saline was administered intraperitoneally to HIV-Tg or wild type (WT) littermates and kidneys were collected 18 hours later. Expression of transporters and cytokines were measured by qRT-PCR and Western blots. Serum cytokine levels were measured by ELISA. Endotoxin induced serum levels of IL-6, TNF-α and IFN-γ in both HIV-Tg and WT animals. The basal mRNA expression of Oct2, Oct3, Octn1, Mate1, Urat1 and Ent1was significantly lower (33-60%) and the expression of Ent2 and Pept2 was significantly higher (33-45%) in HIV-Tg as compared to WT. While endotoxin significantly downregulated the mRNA expression of Mdra1 and Pept2 in both HIV and WT groups (69-78%), it imposed a significant reduction on the mRNA expression of Oct2, Oct3, Octn1,...Continue Reading

Citations

Feb 1, 2019·Parasite Immunology·Najwa NajjarMicheline Piquette-Miller
Oct 3, 2020·Pharmacoepidemiology and Drug Safety·Francis KalemeeraTimothy Rennie
Nov 27, 2019·Pharmaceutics·Navaz Karimian PourMicheline Piquette-Miller
Oct 26, 2020·The AAPS Journal·Dea KojovicMicheline Piquette-Miller

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