Activity of D-carnitine and its derivatives on Trypanosoma infections in rats and mice.
Little progress has been made in the treatment of African trypanosomiasis over the past decades. L-carnitine has a major role in glycolysis-based energy supply of blood trypanosomes for it stimulates constant ATP production. To investigate whether administration of the isomer D-carnitine could exert a competitive inhibition on the metabolic pathway of the L-form, possibly resulting in parasite replication inhibition, several formulations of this compound were tested on Trypanosoma lewisi and T. brucei rhodesiense in rodent models. High oral dosages of D-cornitine inner salt and proprionyl-D-carnitine were not toxic to animals and induced about 50% parasite growth inhibition in reversible, i.e. competitive, fashion. A putative mechanism could be an interference in pyruvate kinase activity and hence ATP production. Considering both, lack of toxicity and inhibitory activity, D-carnitine may have a role in the treatment of African trypanosomiasis, in association with available trypanocidal drugs.
Manganaro
M
M
Department of Infectious Diseases, University of Rome La Sapienza, Rome, Italy.
Mascellino
M T
MT
Gradoni
L
L
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D001921:Brain / Q000473:pathology; D002331:Carnitine / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006019:Glycolysis; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000473:pathology; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D014350:Trypanosoma lewisi / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000473:pathology
D000255:Adenosine Triphosphate; D011770:Pyruvate Kinase; D002331:Carnitine