Chloroquine resistance in the human malaria parasite, Plasmodium falciparum, arises from decreased accumulation of the drug in the ;digestive vacuole' of the parasite, an acidic compartment in which chloroquine exerts its primary toxic effect. It has been proposed that changes in the pH of the digestive vacuole might underlie the decreased accumulation of chloroquine by chloroquine-resistant pa...

An Aotus-Plasmodium falciparum model was used to determine if chloroquine resistance could be reversed in vivo. The putative resistance modulators tested all reverse chloroquine resistance in vitro and included verapamil, chlorpromazine, prochlorperazine, cyproheptadine, ketotifen, a tiapamil analog (Ro 11-2933), and a chlorpromazine analog (SKF 2133-A). Combinations of chloroquine plus chlorpr...

BACKGROUND Due to development of multidrug-resistant Plasmodium falciparum new antimalarial therapies are needed. In Guinea-Bissau, routinely used triple standard-dose chloroquine remained effective for decades despite the existence of "chloroquine-resistant" P. falciparum. This study aimed to determine the in vivo efficacy of higher chloroquine concentrations against P. falciparum with resista...

The antimalarial drug chloroquine is eliminated to a significant extent by renal tubular secretion. The molecular mechanism of renal chloroquine secretion remains unknown. We hypothesized that organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1), localized in the basolateral and luminal membranes of proximal tubule cells, respectively, are involved in chloroqu...

In vivo and in vitro assessments of the response of P. falciparum to chloroquine using WHO standard kits and techniques were carried out in I ran Shahr, Sistan and Baluchestan province of Iran in 1985. In the in vivo assessment, 24 malaria patients treated with chloroquine (25mg/kg over three days) were followed up for one to four weeks. The mean parasite clearance time was 4.3 days and in...

The degradation of cellular proteins in fibroblasts, both those of rapid and those of slow turnover rates, was inhibited by low concentrations of chloroquine or neutral red in the medium. Cells inhibited by chloroquine can be inhibited further by fluoride. Chloroquine was taken up by the fibroblasts and the concentration in the cells reached several hundred times that in the medium. Isopycnic f...

The emergence of chloroquine resistance in Plasmodium falciparum has necessitated the development of alternate strategies for chemotherapy and chemoprophylaxis. One approach has been the identification of drugs that do not possess any intrinsic antimalarial activity when used alone but that potentiate the effect of currently available antimalarial drugs, such as chloroquine. We identified fluox...

Chloroquine, which is a widely used antimalarial drug, has been reported to exert anticancer activity in some tumor types; however, its potential effects on oral squamous cell carcinoma (OSCC) remain unclear. The present study aimed to explore the effects and possible underlying mechanisms of chloroquine against OSCC. MTT and clonogenic assays were conducted to evaluate the effects of chloroqui...

Background: The emergence and spread of chloroquine resistant Plasmodium falciparum in the world stimulated some investigators to consider different aspects of chloroquine resistance in human and rodent Plasmodia. Using animal Plasmodia, particularly primate and rodent Plasmodia can be useful model for human Plasmodia studies. In this study we have tried to consider and compare the sequence of ...

Human erythrocytes were treated with menadione to oxidatively denature hemoglobin and release ferriprotoporphyrin IX (ferriheme, FP) intracellularly. The high affinity of FP for chloroquine was used to detect its release. After incubation for 1 hr at 37 degrees C and pH 7.4 with 0.5 mM menadione, erythrocytes bound 14C-chloroquine with an apparent dissociation constant of 10(-6)M. Untreated ery...