Experimental treatment of Neospora caninum-infected mice with the arylimidamide DB750 and the thiazolide nitazoxanide

Karim Debache, Christophe Guionaud, Christian Kropf, David Boykin, Chad E. Stephens, Andrew Hemphill

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The cationic arylimidamide DB750 and the thiazolide nitazoxanide had been shown earlier to be effective against Neospora caninum tachyzoites in vitro with an IC 50 of 160nM and 4.23μM, respectively. In this study, we have investigated the effects of DB750 and nitazoxanide treatments of experimentally infected Balb/c mice, by applying the drugs either through the oral or the intraperitoneal route. In experiment 1, administration of DB750 (2mg/kg/day) and nitazoxanide (150mg/kg/day) started already 3days prior to experimental infection of mice with 2×10 6 tachyzoites. Following infection, the drugs were further administrated daily for a period of 2weeks, either orally or intraperitoneally. Intraperitoneal injection of DB750 was well tolerated by the mice, but treatment with nitazoxanide resulted in death of all mice within 3days. Upon intraperitoneal application of DB750, the cerebral parasite load was significantly reduced compared to all other groups, while oral application of DB750 and nitazoxanide were not as effective, and resulted in significant weight loss. In experiment 2, mice were infected with 2×10 6 tachyzoites and at 2weeks post-infection, DB750 (2mg/kg/day) was applied by intraperitoneal injections for 14days. In the DB750-treated group, only 2 out of 12 mice succumbed to infection, compared to 7 out of 12 mice in the placebo-group. DB750 treatment also resulted in significantly reduced cerebral parasite burden, and reduced numbers of viable tachyzoites. Our data suggest that DB750 exerted its activity also after crossing the blood-brain barrier, and that this class of compounds could be promising for the control of N. caninum-associated disease.

Original languageEnglish (US)
Pages (from-to)95-100
Number of pages6
JournalExperimental Parasitology
Volume129
Issue number2
DOIs
StatePublished - Oct 1 2011

Fingerprint

nitazoxanide
Neospora
Infection
Intraperitoneal Injections
Therapeutics
Parasite Load
Blood-Brain Barrier
Pharmaceutical Preparations
Weight Loss

Keywords

  • Arylimidamides
  • Cerebral infection
  • Chemotherapy
  • DB750
  • Neospora caninum
  • Neosporosis
  • Nitazoxanide
  • Thiazolides

ASJC Scopus subject areas

  • Parasitology
  • Immunology
  • Infectious Diseases

Cite this

Experimental treatment of Neospora caninum-infected mice with the arylimidamide DB750 and the thiazolide nitazoxanide. / Debache, Karim; Guionaud, Christophe; Kropf, Christian; Boykin, David; Stephens, Chad E.; Hemphill, Andrew.

In: Experimental Parasitology, Vol. 129, No. 2, 01.10.2011, p. 95-100.

Research output: Contribution to journalArticle

Debache, Karim ; Guionaud, Christophe ; Kropf, Christian ; Boykin, David ; Stephens, Chad E. ; Hemphill, Andrew. / Experimental treatment of Neospora caninum-infected mice with the arylimidamide DB750 and the thiazolide nitazoxanide. In: Experimental Parasitology. 2011 ; Vol. 129, No. 2. pp. 95-100.
@article{ef885be129ee4396b6ceeef59125fc3b,
title = "Experimental treatment of Neospora caninum-infected mice with the arylimidamide DB750 and the thiazolide nitazoxanide",
abstract = "The cationic arylimidamide DB750 and the thiazolide nitazoxanide had been shown earlier to be effective against Neospora caninum tachyzoites in vitro with an IC 50 of 160nM and 4.23μM, respectively. In this study, we have investigated the effects of DB750 and nitazoxanide treatments of experimentally infected Balb/c mice, by applying the drugs either through the oral or the intraperitoneal route. In experiment 1, administration of DB750 (2mg/kg/day) and nitazoxanide (150mg/kg/day) started already 3days prior to experimental infection of mice with 2×10 6 tachyzoites. Following infection, the drugs were further administrated daily for a period of 2weeks, either orally or intraperitoneally. Intraperitoneal injection of DB750 was well tolerated by the mice, but treatment with nitazoxanide resulted in death of all mice within 3days. Upon intraperitoneal application of DB750, the cerebral parasite load was significantly reduced compared to all other groups, while oral application of DB750 and nitazoxanide were not as effective, and resulted in significant weight loss. In experiment 2, mice were infected with 2×10 6 tachyzoites and at 2weeks post-infection, DB750 (2mg/kg/day) was applied by intraperitoneal injections for 14days. In the DB750-treated group, only 2 out of 12 mice succumbed to infection, compared to 7 out of 12 mice in the placebo-group. DB750 treatment also resulted in significantly reduced cerebral parasite burden, and reduced numbers of viable tachyzoites. Our data suggest that DB750 exerted its activity also after crossing the blood-brain barrier, and that this class of compounds could be promising for the control of N. caninum-associated disease.",
keywords = "Arylimidamides, Cerebral infection, Chemotherapy, DB750, Neospora caninum, Neosporosis, Nitazoxanide, Thiazolides",
author = "Karim Debache and Christophe Guionaud and Christian Kropf and David Boykin and Stephens, {Chad E.} and Andrew Hemphill",
year = "2011",
month = "10",
day = "1",
doi = "10.1016/j.exppara.2011.07.010",
language = "English (US)",
volume = "129",
pages = "95--100",
journal = "Experimental Parasitology",
issn = "0014-4894",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Experimental treatment of Neospora caninum-infected mice with the arylimidamide DB750 and the thiazolide nitazoxanide

AU - Debache, Karim

AU - Guionaud, Christophe

AU - Kropf, Christian

AU - Boykin, David

AU - Stephens, Chad E.

AU - Hemphill, Andrew

PY - 2011/10/1

Y1 - 2011/10/1

N2 - The cationic arylimidamide DB750 and the thiazolide nitazoxanide had been shown earlier to be effective against Neospora caninum tachyzoites in vitro with an IC 50 of 160nM and 4.23μM, respectively. In this study, we have investigated the effects of DB750 and nitazoxanide treatments of experimentally infected Balb/c mice, by applying the drugs either through the oral or the intraperitoneal route. In experiment 1, administration of DB750 (2mg/kg/day) and nitazoxanide (150mg/kg/day) started already 3days prior to experimental infection of mice with 2×10 6 tachyzoites. Following infection, the drugs were further administrated daily for a period of 2weeks, either orally or intraperitoneally. Intraperitoneal injection of DB750 was well tolerated by the mice, but treatment with nitazoxanide resulted in death of all mice within 3days. Upon intraperitoneal application of DB750, the cerebral parasite load was significantly reduced compared to all other groups, while oral application of DB750 and nitazoxanide were not as effective, and resulted in significant weight loss. In experiment 2, mice were infected with 2×10 6 tachyzoites and at 2weeks post-infection, DB750 (2mg/kg/day) was applied by intraperitoneal injections for 14days. In the DB750-treated group, only 2 out of 12 mice succumbed to infection, compared to 7 out of 12 mice in the placebo-group. DB750 treatment also resulted in significantly reduced cerebral parasite burden, and reduced numbers of viable tachyzoites. Our data suggest that DB750 exerted its activity also after crossing the blood-brain barrier, and that this class of compounds could be promising for the control of N. caninum-associated disease.

AB - The cationic arylimidamide DB750 and the thiazolide nitazoxanide had been shown earlier to be effective against Neospora caninum tachyzoites in vitro with an IC 50 of 160nM and 4.23μM, respectively. In this study, we have investigated the effects of DB750 and nitazoxanide treatments of experimentally infected Balb/c mice, by applying the drugs either through the oral or the intraperitoneal route. In experiment 1, administration of DB750 (2mg/kg/day) and nitazoxanide (150mg/kg/day) started already 3days prior to experimental infection of mice with 2×10 6 tachyzoites. Following infection, the drugs were further administrated daily for a period of 2weeks, either orally or intraperitoneally. Intraperitoneal injection of DB750 was well tolerated by the mice, but treatment with nitazoxanide resulted in death of all mice within 3days. Upon intraperitoneal application of DB750, the cerebral parasite load was significantly reduced compared to all other groups, while oral application of DB750 and nitazoxanide were not as effective, and resulted in significant weight loss. In experiment 2, mice were infected with 2×10 6 tachyzoites and at 2weeks post-infection, DB750 (2mg/kg/day) was applied by intraperitoneal injections for 14days. In the DB750-treated group, only 2 out of 12 mice succumbed to infection, compared to 7 out of 12 mice in the placebo-group. DB750 treatment also resulted in significantly reduced cerebral parasite burden, and reduced numbers of viable tachyzoites. Our data suggest that DB750 exerted its activity also after crossing the blood-brain barrier, and that this class of compounds could be promising for the control of N. caninum-associated disease.

KW - Arylimidamides

KW - Cerebral infection

KW - Chemotherapy

KW - DB750

KW - Neospora caninum

KW - Neosporosis

KW - Nitazoxanide

KW - Thiazolides

UR - http://www.scopus.com/inward/record.url?scp=80052420669&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052420669&partnerID=8YFLogxK

U2 - 10.1016/j.exppara.2011.07.010

DO - 10.1016/j.exppara.2011.07.010

M3 - Article

C2 - 21803039

AN - SCOPUS:80052420669

VL - 129

SP - 95

EP - 100

JO - Experimental Parasitology

JF - Experimental Parasitology

SN - 0014-4894

IS - 2

ER -