Ferriprotoporphyrin IX: a mediator of the antimalarial action of oxidants and 4-aminoquinoline drugs.
Prog Clin Biol Res
; 155: 119-30, 1984.
Article
in En
| MEDLINE
| ID: mdl-6382310
ABSTRACT
Ferriprotoporphyrin IX (FP) is released from hemoglobin by oxidative denaturation or by proteolytic degradation. FP added exogenously to cells or released intracellularly is a lytic toxin. Chloroquine enhances the accumulation of exogenous FP in cellular membranes and potentiates its lytic effect. Menadione is an example of an oxidant drug that denatures hemoglobin, releases FP intracellularly, and thereby lyses cells. Chloroquine increases the accumulation of FP in the membranes of menadione-treated erythrocytes and enhances the hemolysis induced by menadione. Intraerythrocytic malaria parasites release FP from hemoglobin by proteolytic degradation, but they ordinarily survive the exposure either because FP interacts with a soluble intracellular substance, which renders it nontoxic, or because FP is sequestered in an innocuous, insoluble form in malaria pigment. Chloroquine binds tightly to FP, diverts it away from the soluble detoxifying substance in malaria parasites, and delays its sequestration into malarial pigment. Malaria parasites exposed to chloroquine while degrading hemoglobin accumulate a chloroquine-FP complex, which is sufficiently toxic to kill them. FP has a detergent-like effect on biological membranes which may account for its lytic toxicity.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vitamin K
/
Erythrocytes
/
Aminoquinolines
/
Heme
/
Hemin
/
Malaria
/
Antimalarials
Limits:
Animals
Language:
En
Journal:
Prog Clin Biol Res
Year:
1984
Document type:
Article
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA