Arteether (AE) is primarily deethylated to dihydroqinghaosu (DQHS) in rats and humans. Conversion of AE to DQHS was impaired in microsomes from rats infected with Plasmodium berghei. The Km for AE was 175.1 +/- 49.1 and 124.4 +/- 115.1 mumol/l, and Vmax was 2.24 +/- 0.45 and 1.22 +/- 0.67 nmol AE formed/mg protein/min in control and infected microsomes (p < 0.05), respectively. Calculated intrinsic clearance (CLint = initial Vmax/Km) for AE was only 4% lower in infected microsomes. Apparent pharmacokinetic parameter estimates for AE using the isolated perfused rat liver demonstrated no differences (p > 0.05) in volume of distribution, clearance, and half-life between normal and infected animals. Malaria infection resulted in decreased biliary excretion of free AE and DQHS. The majority of AE is eliminated via biliary excretion of conjugated DQHS, which is approximately 500-fold higher than free DQHS and 75-fold higher than free AE on a molar basis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1159/000139496 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection, with resistance to antimalarial drugs, including artemisinin-based combination therapies(ACTs), posing a significant threat. CD4+ naive cells expressing CCR7 are known to play a protective role, as they readily migrate to secondary lymphoid tissues activated by CCL19 chemokines. In an effort to address this challenge, we investigated the impact of Annona muricata, an herbaceous and immunomodulatory plant, on CCL19 concentration.
View Article and Find Full Text PDFSequestration of parasites in the placental vasculature causes increased morbidity and mortality in pregnant compared to non-pregnant patients in malaria- endemic regions. In this study, outbred pregnant CD1 mice with semi allogeneic fetuses were infected with transgenic or mock-inoculated by mosquito bite at either embryonic day (E) 6 (first trimester-equivalent) or 10 (second trimester- equivalent) and compared with non-pregnant females. -infected mosquitoes had greater biting avidity for E10 dams than uninfected mosquitoes, which was not apparent for E6 dams nor non-pregnant females.
View Article and Find Full Text PDFConstitutive expression of Cas9 and rapamycin-inducible Cre recombinase facilitates conditional genome editing in Plasmodium berghei.
Sci Rep
January 2025
Sorbonne Université, CNRS, Inserm, Centre d'Immunologie et des Maladies Infectieuses, CIMI, F-75013 Paris, France.
Malaria is caused by protozoan parasites of the genus Plasmodium and remains a global health concern. The parasite has a highly adaptable life cycle comprising successive rounds of asexual replication in a vertebrate host and sexual maturation in the mosquito vector Anopheles. Genetic manipulation of the parasite has been instrumental for deciphering the function of Plasmodium genes.
View Article and Find Full Text PDFA scalable CRISPR-Cas9 gene editing system facilitates CRISPR screens in the malaria parasite Plasmodium berghei.
Nucleic Acids Res
January 2025
The Laboratory for Molecular Infection Medicine Sweden, Umeå University, Försörjningsvägen 2A, 901 87 Umeå, Sweden.
Many Plasmodium genes remain uncharacterized due to low genetic tractability. Previous large-scale knockout screens have only been able to target about half of the genome in the more genetically tractable rodent malaria parasite Plasmodium berghei. To overcome this limitation, we have developed a scalable CRISPR system called P.
View Article and Find Full Text PDFSynergistic Interaction of Chloroquine with Semipolar Extract Against : Histopathological and Immunological Studies in a Mouse Model.
Iran J Pharm Res
September 2024
Department of Parasitology and Mycology, Skin Diseases and Leishmaniasis Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Background: Malaria parasites have gradually developed resistance to commonly used antimalarial drugs. For decades, chloroquine was the most widely used drug to eradicate malaria. However, with the spread of chloroquine resistance, many countries have adopted combination therapies that utilize two drugs acting synergistically instead of monotherapy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!