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Beneficial effect of aurothiomalate on murine malaria.

Alesutan I, Bobbala D, Qadri SM, Estremera A, Föller M, Lang F - Malar. J. (2010)

Bottom Line: Exposure to aurothiomalate significantly decreased the in vitro parasitemia of P. falciparum-infected human erythrocytes without influencing the intraerythrocytic DNA/RNA content.All nontreated mice died within 30 days of infection.Sodium aurothiomalate influences the survival of Plasmodium berghei-infected mice, an effect only partially explained by stimulation of eryptosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, University of Tübingen, Gmelinstr, 5, 72076 Tübingen, Germany.

ABSTRACT

Background: Premature death of Plasmodium-infected erythrocytes is considered to favourably influence the clinical course of malaria. Aurothiomalate has previously been shown to trigger erythrocyte death or eryptosis, which is characterized by cell membrane scrambling leading to phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing cells are rapidly cleared from circulating blood. The present study thus tested whether sodium aurothiomalate influences the intraerythrocytic parasite development in vitro and the clinical course of murine malaria in vivo.

Methods: Human erythrocytes were infected with Plasmodium falciparum BinH in vitro and mice were infected (intraperitoneal injection of 1 x 106 parasitized murine erythrocytes) with Plasmodium berghei ANKA in vivo.

Results: Exposure to aurothiomalate significantly decreased the in vitro parasitemia of P. falciparum-infected human erythrocytes without influencing the intraerythrocytic DNA/RNA content. Administration of sodium aurothiomalate in vivo (daily 10 mg/kg b.w. s.c. from the 8th day of infection) enhanced the percentage of phosphatidylserine-exposing infected and noninfected erythrocytes in blood. All nontreated mice died within 30 days of infection. Aurothiomalate-treatment delayed the lethal course of malaria leading to survival of more than 50% of the mice 30 days after infection.

Conclusions: Sodium aurothiomalate influences the survival of Plasmodium berghei-infected mice, an effect only partially explained by stimulation of eryptosis.

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Effects of sodium aurothiomalate on intraerythrocytic amplification and in vitro parasitemia. A. In vitro parasitemia with P. falciparum (left panel) in human erythrocytes as a function of the aurothiomalate concentration (arithmetic means ± SEM, n = 16). *, *** indicate significant difference (p < 0.05, p < 0.001) from the absence of aurothiomalate. Intraerythrocytic DNA amplification (right panel) as a function of the aurothiomalate concentration (arithmetic means ± SEM, n = 12). B. Intraerythrocytic DNA amplification (right panel) as in B for different time periods (arithmetic means ± SEM, n = 8).
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Figure 1: Effects of sodium aurothiomalate on intraerythrocytic amplification and in vitro parasitemia. A. In vitro parasitemia with P. falciparum (left panel) in human erythrocytes as a function of the aurothiomalate concentration (arithmetic means ± SEM, n = 16). *, *** indicate significant difference (p < 0.05, p < 0.001) from the absence of aurothiomalate. Intraerythrocytic DNA amplification (right panel) as a function of the aurothiomalate concentration (arithmetic means ± SEM, n = 12). B. Intraerythrocytic DNA amplification (right panel) as in B for different time periods (arithmetic means ± SEM, n = 8).

Mentions: A first series of experiments explored the influence of aurothiomalate on the in vitro growth of Plasmodium falciparum in human erythrocytes. To this end, P. falciparum-infected erythrocytes were cultured in human erythrocytes and synchronized to the ring stage by sorbitol treatment. Within 48 hours the percentage of infected erythrocytes increased from 6.0% to 21.0% in the absence and to 9.8% in the presence of 100 μM aurothiomalate (Fig. 1A). Accordingly, aurothiomalate blunted the increase in the percentage of parasitized erythrocytes, an effect reaching statistical significance at ≥ 10 μM aurothiomalate (Fig. 1A). The halfmaximal inhibition (IC50) was achieved by 68 μM aurothiomalate. In contrast, at the concentrations tested, the presence of aurothiomalate did not influence the intraerythrocytic DNA amplification of the parasite (Fig. 1AB).


Beneficial effect of aurothiomalate on murine malaria.

Alesutan I, Bobbala D, Qadri SM, Estremera A, Föller M, Lang F - Malar. J. (2010)

Effects of sodium aurothiomalate on intraerythrocytic amplification and in vitro parasitemia. A. In vitro parasitemia with P. falciparum (left panel) in human erythrocytes as a function of the aurothiomalate concentration (arithmetic means ± SEM, n = 16). *, *** indicate significant difference (p < 0.05, p < 0.001) from the absence of aurothiomalate. Intraerythrocytic DNA amplification (right panel) as a function of the aurothiomalate concentration (arithmetic means ± SEM, n = 12). B. Intraerythrocytic DNA amplification (right panel) as in B for different time periods (arithmetic means ± SEM, n = 8).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875225&req=5

Figure 1: Effects of sodium aurothiomalate on intraerythrocytic amplification and in vitro parasitemia. A. In vitro parasitemia with P. falciparum (left panel) in human erythrocytes as a function of the aurothiomalate concentration (arithmetic means ± SEM, n = 16). *, *** indicate significant difference (p < 0.05, p < 0.001) from the absence of aurothiomalate. Intraerythrocytic DNA amplification (right panel) as a function of the aurothiomalate concentration (arithmetic means ± SEM, n = 12). B. Intraerythrocytic DNA amplification (right panel) as in B for different time periods (arithmetic means ± SEM, n = 8).
Mentions: A first series of experiments explored the influence of aurothiomalate on the in vitro growth of Plasmodium falciparum in human erythrocytes. To this end, P. falciparum-infected erythrocytes were cultured in human erythrocytes and synchronized to the ring stage by sorbitol treatment. Within 48 hours the percentage of infected erythrocytes increased from 6.0% to 21.0% in the absence and to 9.8% in the presence of 100 μM aurothiomalate (Fig. 1A). Accordingly, aurothiomalate blunted the increase in the percentage of parasitized erythrocytes, an effect reaching statistical significance at ≥ 10 μM aurothiomalate (Fig. 1A). The halfmaximal inhibition (IC50) was achieved by 68 μM aurothiomalate. In contrast, at the concentrations tested, the presence of aurothiomalate did not influence the intraerythrocytic DNA amplification of the parasite (Fig. 1AB).

Bottom Line: Exposure to aurothiomalate significantly decreased the in vitro parasitemia of P. falciparum-infected human erythrocytes without influencing the intraerythrocytic DNA/RNA content.All nontreated mice died within 30 days of infection.Sodium aurothiomalate influences the survival of Plasmodium berghei-infected mice, an effect only partially explained by stimulation of eryptosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, University of Tübingen, Gmelinstr, 5, 72076 Tübingen, Germany.

ABSTRACT

Background: Premature death of Plasmodium-infected erythrocytes is considered to favourably influence the clinical course of malaria. Aurothiomalate has previously been shown to trigger erythrocyte death or eryptosis, which is characterized by cell membrane scrambling leading to phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing cells are rapidly cleared from circulating blood. The present study thus tested whether sodium aurothiomalate influences the intraerythrocytic parasite development in vitro and the clinical course of murine malaria in vivo.

Methods: Human erythrocytes were infected with Plasmodium falciparum BinH in vitro and mice were infected (intraperitoneal injection of 1 x 106 parasitized murine erythrocytes) with Plasmodium berghei ANKA in vivo.

Results: Exposure to aurothiomalate significantly decreased the in vitro parasitemia of P. falciparum-infected human erythrocytes without influencing the intraerythrocytic DNA/RNA content. Administration of sodium aurothiomalate in vivo (daily 10 mg/kg b.w. s.c. from the 8th day of infection) enhanced the percentage of phosphatidylserine-exposing infected and noninfected erythrocytes in blood. All nontreated mice died within 30 days of infection. Aurothiomalate-treatment delayed the lethal course of malaria leading to survival of more than 50% of the mice 30 days after infection.

Conclusions: Sodium aurothiomalate influences the survival of Plasmodium berghei-infected mice, an effect only partially explained by stimulation of eryptosis.

Show MeSH
Related in: MedlinePlus