P. berghei ANKA Experimental Malaria Infection Alters Drug Transporter and Drug Metabolizing Enzyme Expression in Pregnancy
Year: 2012
Type: dissertation
Abstract: A P. berghei ANKA mouse model of malaria infection was employed to investigate disease-induced changes in an array of genes that impact drug disposition in pregnancy. We demonstrate the reduced expression of a number of transporters in the placenta of infected dams relative to uninfected dams, in addition to altered expression of transporters and Cyp3a11 in maternal and fetal tissues. The impact of Complement 5a receptor (C5aR) activation during malaria infection on transporter expression in liver and placenta was also examined in C5aR-/- infected dams. Increased expression of Abcb1a and Abcg2 in the placenta of C5aR-/- infected dams was observed when compared to wildtype-infected dams. Furthermore, whereas expression of placental Abcb1a and Abc1b were decreased in infected wildtype dams, their expression was unchanged in C5aR-/- infected dams. Collectively, if these findings translate to malaria infection in human pregnancy, the systemic clearance and maternofetal disposition of therapeutics and other xenobiotics may be altered.
Source: TSpace (University of Toronto)
Author: Alexander M Cressman
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2623887535