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Purification of Extracellular Trypanosomes, Including African, from Blood by Anion-Exchangers (Diethylaminoethyl-cellulose Columns)
Published on: April 6, 2019
Activity of D-carnitine and its derivatives on Trypanosoma infections in rats and mice
M Manganaro1, M T Mascellino, L Gradoni
1Department of Infectious Diseases, University of Rome La Sapienza, Rome, Italy.
Abstract:
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.
Insights
D-carnitine shows promise for treating African trypanosomiasis. It competitively inhibits parasite growth by interfering with energy production, offering a potential new therapeutic strategy with low toxicity.
Area of Science:
- Parasitology
- Biochemistry
- Pharmacology
Background:
- African trypanosomiasis treatment has seen limited advancement.
- L-carnitine is crucial for trypanosome energy metabolism (ATP production).
Purpose of the Study:
- To investigate D-carnitine's potential to inhibit Trypanosoma parasite replication.
- To explore D-carnitine as a competitive inhibitor of L-carnitine's metabolic pathway.
Main Methods:
- Testing D-carnitine formulations in rodent models infected with Trypanosoma lewisi and T. brucei rhodesiense.
- Assessing toxicity and parasite growth inhibition.
Main Results:
- High oral doses of D-carnitine were non-toxic to rodents.
- D-carnitine induced approximately 50% reversible parasite growth inhibition.
- A potential mechanism involves interference with pyruvate kinase activity and ATP production.
Conclusions:
- D-carnitine demonstrates non-toxic, competitive inhibition of African trypanosome growth.
- D-carnitine may serve as an adjunct therapy for African trypanosomiasis alongside existing drugs.
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