Artemisone and Artemiside Control Acute and Reactivated Toxoplasmosis in a Murine Model

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2009 Jul 29

PMID 19635951

Citations 39

Authors

Ildiko R Dunay

Wing Chi Chan

Richard K Haynes

L David Sibley

Affiliations

Soon will be listed here.

Abstract

Immunocompromised patients are at risk of developing toxoplasmosis, and although chemotherapy is available, standard treatments are often complicated by severe side effects. Artemisinin is a new highly potent antimalarial drug that has activity against Toxoplasma gondii in vitro. However, artemisinin derivatives have previously been ineffective in vivo using a rat model of toxoplasmosis. In the present study, the efficacy of several new artemisinin derivates was investigated for treatment of mice infected with the parasite Toxoplasma gondii. Artemiside and artemisone displayed better inhibition than either artemisinin or artesunate against the parasite in vitro. Artemiside and artemisone treatment controlled parasite replication in vivo, and mice survived the acute infection. In a murine model of reactivated toxoplasmosis, both drugs increased survival, although artemiside was more effective. These results indicate that these newer derivatives of artemisinin may have potential for treatment of toxoplasmosis.

Citing Articles

The Search for Drugs Derived from Natural Products for Infection Treatment in the Last 20 Years - A Systematic Review.

Marques-Santos F, Xavier Faria R, Amendoeira M Curr Top Med Chem. 2024; 24(22):1960-1999.

PMID: 38952156 DOI: 10.2174/0115680266299409240606062235.

Single and combination treatment of Toxoplasma gondii infections with a bumped kinase inhibitor and artemisone in vitro and with artemiside in experimentally infected mice.

Schlange C, Muller J, Imhof D, Hanggeli K, Boubaker G, Ortega-Mora L Exp Parasitol. 2023; 255:108655.

PMID: 37981259 PMC: 11585351. DOI: 10.1016/j.exppara.2023.108655.

Artemisinin derivatives induce oxidative stress leading to DNA damage and caspase-mediated apoptosis in Theileria annulata-transformed cells.

Barman M, Dandasena D, Suresh A, Bhandari V, Kamble S, Singh S Cell Commun Signal. 2023; 21(1):78.

PMID: 37069625 PMC: 10111749. DOI: 10.1186/s12964-023-01067-7.

Treatment of Murine Toxoplasmosis with Oral and Parenteral Artemether and Following by Detection of Gene by Quantitative Real-Time PCR (qPCR) for Evaluating Parasite Density.

Mikaeiloo H, Ghaffarifar F, Dalimi A, Zuhair Hassan M, Sharifi Z Iran J Parasitol. 2022; 17(1):53-61.

PMID: 36046558 PMC: 9375721. DOI: 10.18502/ijpa.v17i1.9016.

Absinthe against multi-drug resistant bacterial pathogens? A recent update on the antibacterial effects of Artemisia compounds.

Janz J, Shayya N, Bereswill S, Heimesaat M Eur J Microbiol Immunol (Bp). 2022; .

PMID: 35471952 PMC: 9630932. DOI: 10.1556/1886.2022.00007.

References

SEEBER F, Boothroyd J . Escherichia coli beta-galactosidase as an in vitro and in vivo reporter enzyme and stable transfection marker in the intracellular protozoan parasite Toxoplasma gondii. Gene. 1996; 169(1):39-45. DOI: 10.1016/0378-1119(95)00786-5. View

Nagamune K, Moreno S, Sibley L . Artemisinin-resistant mutants of Toxoplasma gondii have altered calcium homeostasis. Antimicrob Agents Chemother. 2007; 51(11):3816-23. PMC: 2151471. DOI: 10.1128/AAC.00582-07. View

Haynes R, Krishna S . Artemisinins: activities and actions. Microbes Infect. 2004; 6(14):1339-46. DOI: 10.1016/j.micinf.2004.09.002. View

Silveira C, Belfort Jr R, Muccioli C, Abreu M, Martins M, Victora C . A follow-up study of Toxoplasma gondii infection in southern Brazil. Am J Ophthalmol. 2001; 131(3):351-4. DOI: 10.1016/s0002-9394(00)00830-8. View

Jones J, Muccioli C, Belfort Jr R, Holland G, Roberts J, Silveira C . Recently acquired Toxoplasma gondii infection, Brazil. Emerg Infect Dis. 2006; 12(4):582-7. PMC: 3294697. DOI: 10.3201/eid1204.051081. View

Araujo F, Huskinson J, Remington J . Remarkable in vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against tachyzoites and tissue cysts of Toxoplasma gondii. Antimicrob Agents Chemother. 1991; 35(2):293-9. PMC: 244994. DOI: 10.1128/AAC.35.2.293. View

Megged O, Shalit I, Yaniv I, Stein J, Fisher S, Levy I . Breakthrough cerebral toxoplasmosis in a patient receiving atovaquone prophylaxis after a hematopoietic stem cell transplantation. Pediatr Transplant. 2008; 12(8):902-5. DOI: 10.1111/j.1399-3046.2007.00891.x. View

Ajzenberg D, Cogne N, Paris L, Bessieres M, Thulliez P, Filisetti D . Genotype of 86 Toxoplasma gondii isolates associated with human congenital toxoplasmosis, and correlation with clinical findings. J Infect Dis. 2002; 186(5):684-9. DOI: 10.1086/342663. View

Jones-Brando L, DAngelo J, Posner G, Yolken R . In vitro inhibition of Toxoplasma gondii by four new derivatives of artemisinin. Antimicrob Agents Chemother. 2006; 50(12):4206-8. PMC: 1693994. DOI: 10.1128/AAC.00793-06. View

10.

Wong S, Remington J . Toxoplasmosis in pregnancy. Clin Infect Dis. 1994; 18(6):853-61; quiz 862. DOI: 10.1093/clinids/18.6.853. View

11.

Montoya J, Liesenfeld O . Toxoplasmosis. Lancet. 2004; 363(9425):1965-76. DOI: 10.1016/S0140-6736(04)16412-X. View

12.

Dunay I, Heimesaat M, Bushrab F, Muller R, Stocker H, Arasteh K . Atovaquone maintenance therapy prevents reactivation of toxoplasmic encephalitis in a murine model of reactivated toxoplasmosis. Antimicrob Agents Chemother. 2004; 48(12):4848-54. PMC: 529229. DOI: 10.1128/AAC.48.12.4848-4854.2004. View

13.

DAlessandro S, Gelati M, Basilico N, Parati E, Haynes R, Taramelli D . Differential effects on angiogenesis of two antimalarial compounds, dihydroartemisinin and artemisone: implications for embryotoxicity. Toxicology. 2007; 241(1-2):66-74. DOI: 10.1016/j.tox.2007.08.084. View

14.

McLeod R, Boyer K, Karrison T, Kasza K, Swisher C, Roizen N . Outcome of treatment for congenital toxoplasmosis, 1981-2004: the National Collaborative Chicago-Based, Congenital Toxoplasmosis Study. Clin Infect Dis. 2006; 42(10):1383-94. DOI: 10.1086/501360. View

15.

Ashley E, White N . Artemisinin-based combinations. Curr Opin Infect Dis. 2005; 18(6):531-6. DOI: 10.1097/01.qco.0000186848.46417.6c. View

16.

Baatz H, Mirshahi A, Puchta J, Gumbel H, Hattenbach L . Reactivation of toxoplasma retinochoroiditis under atovaquone therapy in an immunocompetent patient. Ocul Immunol Inflamm. 2006; 14(3):185-7. DOI: 10.1080/09273940600659740. View

17.

Suzuki Y, Joh K . Effect of the strain of Toxoplasma gondii on the development of toxoplasmic encephalitis in mice treated with antibody to interferon-gamma. Parasitol Res. 1994; 80(2):125-30. DOI: 10.1007/BF00933779. View

18.

Haynes R, Fugmann B, Stetter J, Rieckmann K, Heilmann H, Chan H . Artemisone--a highly active antimalarial drug of the artemisinin class. Angew Chem Int Ed Engl. 2006; 45(13):2082-8. DOI: 10.1002/anie.200503071. View

19.

Lehmann T, Marcet P, Graham D, Dahl E, Dubey J . Globalization and the population structure of Toxoplasma gondii. Proc Natl Acad Sci U S A. 2006; 103(30):11423-8. PMC: 1544101. DOI: 10.1073/pnas.0601438103. View

20.

Saeij J, Boyle J, Grigg M, Arrizabalaga G, Boothroyd J . Bioluminescence imaging of Toxoplasma gondii infection in living mice reveals dramatic differences between strains. Infect Immun. 2005; 73(2):695-702. PMC: 547072. DOI: 10.1128/IAI.73.2.695-702.2005. View