Effect of ozonide OZ418 against Schistosoma japonicum harbored in mice

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Abstract

The in vitro and in vivo efficacies of ozonide carboxylic acid OZ418 against Schistosoma japonicum were investigated. For in vitro experiments, juvenile (14-day-old) and adult schistosomes were collected from mice infected with 80-100 S. japonicum cercariae for 14 and 35 days post-infection and the worms were maintained in Roswell Park Memorial Institute (RPMI) 1640 supplemented by 10% calf serum. Against 35-day-old adult S. japonicum, OZ418 resulted in weakened worm motor activity, injury to the worm body, emergence of vacuoles along the worm surface, and death. A similar outcome was seen in 14-day-old juvenile S. japonicum exposed to OZ418. Ineffective concentrations (1, 5, and 10 μg/mL) of OZ418 also interacted with hemin to significantly increase the killing effect against adult schistosomes. The LC50 value of OZ418 against juvenile (14-day-old) and adult schistosomes were identical--16.2 μg/mL, whereas the corresponding LC95 values were 30.7 and 22.7 μg/mL, respectively. Treatment of adult and juvenile (14-day-old) S. japonicum-infected mice with single 200-400-mg/kg oral doses of OZ418 produced total worm burden reductions of 68.5-84.1 and 37.5-50.9%, respectively. Further study showed that in mice infected with various stages of schistosomes and treated with a single oral OZ418 400 mg/kg, poor efficacy was seen in the 3-h-old juvenile worm group, while 14-day-old and 21-day-old juvenile worm groups exhibited less efficacy with total worm burden reductions of 42.6-52.4%. On the other hand, similar and higher total worm burden reductions (64.2-76.0%) were seen in the 7-day-old juvenile worm group and 28-day-old as well as 35-day-old adult worm groups. Furthermore, the mean worm burden reductions of the 7-day-old juvenile worm group and 35-day-old adult worm group were statistically significantly higher than that of the 14-day-old or 21-day-old juvenile worm group (P < 0.01 or <0.05). These data suggest that OZ418 has promising efficacy against 7-day-old juvenile and adult S. japonicum.

Original languageEnglish (US)
Pages (from-to)3259-3266
Number of pages8
JournalParasitology Research
Volume113
Issue number9
DOIs
StatePublished - Sep 1 2014
Externally publishedYes

Fingerprint

Schistosoma japonicum
mice
Schistosoma
Cercaria
Hemin
Carboxylic Acids
Vacuoles
mouth
Motor Activity
1,2,4-trioxane
cercariae
Wounds and Injuries
carboxylic acids
Infection
Serum
lethal concentration 50
vacuoles
calves
death

ASJC Scopus subject areas

  • Parasitology
  • veterinary(all)
  • Insect Science
  • Infectious Diseases

Cite this

Effect of ozonide OZ418 against Schistosoma japonicum harbored in mice. / Xue, Jian; Wang, Xiaofang; Dong, Yuxiang; Vennerstrom, Jonathan L; Xiao, Shu hua.

In: Parasitology Research, Vol. 113, No. 9, 01.09.2014, p. 3259-3266.

Research output: Contribution to journalArticle

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title = "Effect of ozonide OZ418 against Schistosoma japonicum harbored in mice",
abstract = "The in vitro and in vivo efficacies of ozonide carboxylic acid OZ418 against Schistosoma japonicum were investigated. For in vitro experiments, juvenile (14-day-old) and adult schistosomes were collected from mice infected with 80-100 S. japonicum cercariae for 14 and 35 days post-infection and the worms were maintained in Roswell Park Memorial Institute (RPMI) 1640 supplemented by 10{\%} calf serum. Against 35-day-old adult S. japonicum, OZ418 resulted in weakened worm motor activity, injury to the worm body, emergence of vacuoles along the worm surface, and death. A similar outcome was seen in 14-day-old juvenile S. japonicum exposed to OZ418. Ineffective concentrations (1, 5, and 10 μg/mL) of OZ418 also interacted with hemin to significantly increase the killing effect against adult schistosomes. The LC50 value of OZ418 against juvenile (14-day-old) and adult schistosomes were identical--16.2 μg/mL, whereas the corresponding LC95 values were 30.7 and 22.7 μg/mL, respectively. Treatment of adult and juvenile (14-day-old) S. japonicum-infected mice with single 200-400-mg/kg oral doses of OZ418 produced total worm burden reductions of 68.5-84.1 and 37.5-50.9{\%}, respectively. Further study showed that in mice infected with various stages of schistosomes and treated with a single oral OZ418 400 mg/kg, poor efficacy was seen in the 3-h-old juvenile worm group, while 14-day-old and 21-day-old juvenile worm groups exhibited less efficacy with total worm burden reductions of 42.6-52.4{\%}. On the other hand, similar and higher total worm burden reductions (64.2-76.0{\%}) were seen in the 7-day-old juvenile worm group and 28-day-old as well as 35-day-old adult worm groups. Furthermore, the mean worm burden reductions of the 7-day-old juvenile worm group and 35-day-old adult worm group were statistically significantly higher than that of the 14-day-old or 21-day-old juvenile worm group (P < 0.01 or <0.05). These data suggest that OZ418 has promising efficacy against 7-day-old juvenile and adult S. japonicum.",
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T1 - Effect of ozonide OZ418 against Schistosoma japonicum harbored in mice

AU - Xue, Jian

AU - Wang, Xiaofang

AU - Dong, Yuxiang

AU - Vennerstrom, Jonathan L

AU - Xiao, Shu hua

PY - 2014/9/1

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N2 - The in vitro and in vivo efficacies of ozonide carboxylic acid OZ418 against Schistosoma japonicum were investigated. For in vitro experiments, juvenile (14-day-old) and adult schistosomes were collected from mice infected with 80-100 S. japonicum cercariae for 14 and 35 days post-infection and the worms were maintained in Roswell Park Memorial Institute (RPMI) 1640 supplemented by 10% calf serum. Against 35-day-old adult S. japonicum, OZ418 resulted in weakened worm motor activity, injury to the worm body, emergence of vacuoles along the worm surface, and death. A similar outcome was seen in 14-day-old juvenile S. japonicum exposed to OZ418. Ineffective concentrations (1, 5, and 10 μg/mL) of OZ418 also interacted with hemin to significantly increase the killing effect against adult schistosomes. The LC50 value of OZ418 against juvenile (14-day-old) and adult schistosomes were identical--16.2 μg/mL, whereas the corresponding LC95 values were 30.7 and 22.7 μg/mL, respectively. Treatment of adult and juvenile (14-day-old) S. japonicum-infected mice with single 200-400-mg/kg oral doses of OZ418 produced total worm burden reductions of 68.5-84.1 and 37.5-50.9%, respectively. Further study showed that in mice infected with various stages of schistosomes and treated with a single oral OZ418 400 mg/kg, poor efficacy was seen in the 3-h-old juvenile worm group, while 14-day-old and 21-day-old juvenile worm groups exhibited less efficacy with total worm burden reductions of 42.6-52.4%. On the other hand, similar and higher total worm burden reductions (64.2-76.0%) were seen in the 7-day-old juvenile worm group and 28-day-old as well as 35-day-old adult worm groups. Furthermore, the mean worm burden reductions of the 7-day-old juvenile worm group and 35-day-old adult worm group were statistically significantly higher than that of the 14-day-old or 21-day-old juvenile worm group (P < 0.01 or <0.05). These data suggest that OZ418 has promising efficacy against 7-day-old juvenile and adult S. japonicum.

AB - The in vitro and in vivo efficacies of ozonide carboxylic acid OZ418 against Schistosoma japonicum were investigated. For in vitro experiments, juvenile (14-day-old) and adult schistosomes were collected from mice infected with 80-100 S. japonicum cercariae for 14 and 35 days post-infection and the worms were maintained in Roswell Park Memorial Institute (RPMI) 1640 supplemented by 10% calf serum. Against 35-day-old adult S. japonicum, OZ418 resulted in weakened worm motor activity, injury to the worm body, emergence of vacuoles along the worm surface, and death. A similar outcome was seen in 14-day-old juvenile S. japonicum exposed to OZ418. Ineffective concentrations (1, 5, and 10 μg/mL) of OZ418 also interacted with hemin to significantly increase the killing effect against adult schistosomes. The LC50 value of OZ418 against juvenile (14-day-old) and adult schistosomes were identical--16.2 μg/mL, whereas the corresponding LC95 values were 30.7 and 22.7 μg/mL, respectively. Treatment of adult and juvenile (14-day-old) S. japonicum-infected mice with single 200-400-mg/kg oral doses of OZ418 produced total worm burden reductions of 68.5-84.1 and 37.5-50.9%, respectively. Further study showed that in mice infected with various stages of schistosomes and treated with a single oral OZ418 400 mg/kg, poor efficacy was seen in the 3-h-old juvenile worm group, while 14-day-old and 21-day-old juvenile worm groups exhibited less efficacy with total worm burden reductions of 42.6-52.4%. On the other hand, similar and higher total worm burden reductions (64.2-76.0%) were seen in the 7-day-old juvenile worm group and 28-day-old as well as 35-day-old adult worm groups. Furthermore, the mean worm burden reductions of the 7-day-old juvenile worm group and 35-day-old adult worm group were statistically significantly higher than that of the 14-day-old or 21-day-old juvenile worm group (P < 0.01 or <0.05). These data suggest that OZ418 has promising efficacy against 7-day-old juvenile and adult S. japonicum.

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