Modification of oxidative status in Plasmodium berghei-infected erythrocytes by E-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline compared to chloroquine.
E-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline (IQ) is a new quinoline derivative which has been reported as a haemoglobin degradation and ss-haematin formation inhibitor. The haemoglobin proteolysis induced by Plasmodium parasites represents a source of amino acids and haeme, leading to oxidative stress in infected cells. In this paper, we evaluated oxidative status in Plasmodium berghei-infected erythrocytes in the presence of IQ using chloroquine (CQ) as a control. After haemolysis, superoxide dismutase (SOD), catalase, glutathione cycle and NADPH + H+-dependent dehydrogenase enzyme activities were investigated. Lipid peroxidation was also assayed to evaluate lipid damage. The results showed that the overall activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were significantly diminished by IQ (by 53.5% and 100%, respectively). Glutathione peroxidase activity was also lowered (31%) in conjunction with a higher GSSG/GSH ratio. As a compensatory response, overall SOD activity increased and lipid peroxidation decreased, protecting the cells from the haemolysis caused by the infection. CQ shared most of the effects showed by IQ; however it was able to inhibit the activity of isocitrate dehydrogenase and glutathione-S-transferase. In conclusion, IQ could be a candidate for further studies in malaria research interfering with the oxidative status in Plasmodium berghei infection.
Rodrigues
Juan
J
Unidad de Síntesis Orgánica, Facultad de Farmacia, Universidad Central de Venezuela, Caracas, Venezuela. juanricardorodrigues@yahoo.es
Charris
Jaime
J
Domínguez
José
J
Angel
Jorge
J
Gamboa
Neira
N
D000818:Animals; D002738:Chloroquine / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects* / Q000469:parasitology; D015227:Lipid Peroxidation; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects*; D010962:Plasmodium berghei / Q000187:drug effects* / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
C547412:E-2-chloro-8-methyl-3-((4'-methoxy-1'-indanoyl)-2'-methyliden)quinoline; D011804:Quinolines; D002738:Chloroquine; C037219:quinoline; D013482:Superoxide Dismutase