Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
INHIBITION BY ANTIMALARIAL-DRUGS OF HEMOGLOBIN DENATURATION AND IRON RELEASE IN ACIDIFIED RED-BLOOD-CELL LYSATES - A POSSIBLE MECHANISM OF THEIR ANTIMALARIAL EFFECT
Autore:
GABAY T; KRUGLIAK M; SHALMIEV G; GINSBURG H;
Indirizzi:
HEBREW UNIV JERUSALEM,INST LIFE SCI,DEPT BIOL CHEM IL-91904 JERUSALEMISRAEL HEBREW UNIV JERUSALEM,INST LIFE SCI,DEPT BIOL CHEM IL-91904 JERUSALEMISRAEL
Titolo Testata:
Parasitology
, volume: 108, anno: 1994,
parte:, 4
pagine: 371 - 381
SICI:
0031-1820(1994)108:<371:IBAOHD>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
PARASITE PLASMODIUM-FALCIPARUM; QUINOLINE-CONTAINING ANTIMALARIALS; RESISTANT STRAINS; HYDROXYL RADICALS; FOOD VACUOLE; SERUM IRON; HEMOGLOBIN; CHLOROQUINE; AUTOXIDATION; ERYTHROCYTES;
Keywords:
PLASMODIUM FALCIPARUM; HEMOGLOBIN; IRON; CHLOROQUINE; QUININE; MEFLOQUINE; AMODIAQUINE; ASCORBATE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
53
Recensione:
Indirizzi per estratti:
Citazione:
T. Gabay et al., "INHIBITION BY ANTIMALARIAL-DRUGS OF HEMOGLOBIN DENATURATION AND IRON RELEASE IN ACIDIFIED RED-BLOOD-CELL LYSATES - A POSSIBLE MECHANISM OF THEIR ANTIMALARIAL EFFECT", Parasitology, 108, 1994, pp. 371-381

Abstract

Intraerythrocytic malaria parasites ingest the cytosol of their host cell and digest it inside their acid food vacuoles. Acidified (pH 4-5.5, 37 degrees C) human red blood cell lysates were used to simulate this process, measuring the denaturation of haemoglobin (Hb) and the release of iron, in the absence or presence of exogenous protease. Spontaneous Hb denaturation and appearance of non-heme iron were observed upon lysate acidification, their rates decreasing with increasing pH, and increasing in the presence of protease. Both processes were inhibited by the quinoline-containing anti-malarial drugs (QCDs) chloroquine, quinine, mefloquine and amodiaquine at concentrations well below thoseexpected in the acidic food vacuole of the parasite. Spectrophotometric analysis indicated that chloroquine complexes with heme in acid-denatured haemoglobin. Other weak bases as well as verapamil and diltiazem, known to reverse the resistance of malarial parasites to chloroquine, were without effect indicating that the action of QCDs is specific. Based on our previous results and the present report, we suggest thatiron release in acidified lysates is mediated through the formation of ferryl (Fe(IV)) radicals. QCDs possibly complex with this radical, as they do with heme, and prevent its contact with an adjacent heme molecule which is required for ring opening and iron release. These results may suggest that one of the anti-malarial effects of QCDs is to deprive the parasite of an adequate iron supply. Addition of iron to cultures of Plasmodium falciparum um was expected to circumvent the deprivation of Iron and reduce the anti-malarial effect of QCDs. However, adding iron as penetrating fructose or nitrilotriacetate complexes did not alter the parasite's susceptibility to chloroquine. Ascorbate markedly increased the release of iron in acidified lysates, and this effect was not reduced by chloroquine. Ascorbate was found to decrease parasite susceptibility to chloroquine, suggesting that iron deprivation may be an important factor in the antimalarial action of QCDs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 07:28:36