Effect of salinomycin-Na on malaria parasites (Plasmodium falciparum and P. berghei)

In vitro exposure of Plasmodium falciparum and P. berghei to salinomycin-Na showed that 10 min incubation in RPMI 1640 medium containing 100μg/ml of the polyether antibiotic led to complete destruction of most parasites; in media containing 10 or 1 μg/ml salinomycin-Na some young developmental stages seemed to survive, apparently due to the protection of the mostly intact host cell. In vitro treatment of rats infected with P. berghei revealed that a single subcutaneous (oral) dose of 20 mg/kg (80 mg/kg) salinomycin-Na caused complete destruction of parasites. Incipient degeneration of the parasites could be already observed 1 h after treatment. After 22 h parasites had disappeared from blood smears. Repeated subcutaneous doses of the polyether as low as 5 mg/kg (×3) completely destroyed the asexual stages of P. berghei. During the ultrastructural investigation of the action of salinomycin-Na it was found that initially the inner lacunes (such as endoplasmic reticulum and perinuclear space) and the mitochondrion were markedly swollen. This was followed by mitochondrial disruption with rupture of the parasites’ pellicle. Since the infected host cells also ruptured, mainly extracellular parasites were seen in blood smears beginning 6 h after treatment. Salinomycin-Na seems to act similarly on the malarial parasites and on the free merozoites of chicken intestinal coccidia.