The action of salinomycin-Na and lasalocid-Na on chloroquine- and mepacrine-resistant line of Plasmodium berghei K 173-strain in Wistar rats.
Salinomycin-Na and lasalocid-Na, two ionophorous antibiotics known for their anticoccidial activity, exhibit in vivo blood schizontocidal action on the Plasmodium berghei Keyberg 173 RC/M line that has a high level of resistance to chloroquine and mepacrine. Salinomycin was found to have a greater effect than lasalocid on asexual stages of this line. Trophozoites and schizonts were no longer found after a single dose of 20 mg/kg or five doses of 1.25 mg/kg of salinomycin whereas a single dose of 40 mg/kg or five doses of 20 mg/kg of lasalocid showed no marked effect on parasitaemia within 96 h of starting treatment in rats. Some toxicological data show that lasalocid, however, is better tolerated in domestic animals than salinomycin. Early morphological changes in asexual blood stages were membrane-coiling in the cytoplasm followed by vacuolization and disruption of the cell membrane or pellicle after treatment with both compounds. In particular mature schizonts were totally destroyed showing enormously large vacuoles. Toxicological data and blood schizontocidal activity indicate the narrow safety margin in P. berghei infected rats, and place salinomycin in the 'markedly toxic' group of antimalarial compounds.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002462:Cell Membrane / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects; D004352:Drug Resistance, Microbial; D007832:Lasalocid / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D007928:Lethal Dose 50; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D008297:Male; D008854:Microscopy, Electron; D010962:Plasmodium berghei / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D011714:Pyrans / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D000095662:Polyether Polyketides
D000900:Anti-Bacterial Agents; D002738:Chloroquine; D007832:Lasalocid; D011714:Pyrans; D011796:Quinacrine; C010327:salinomycin; D000095662:Polyether Polyketides