Cargando…
Freeze-dried equine-derived redback spider antivenom: a local irritation study by intramuscular injection in rabbits and a repeated-dose toxicity study in rats
The redback spider (Latrodectus hasseltii) is nonindigenous to Japan but has now spread throughout the country. Bites to humans are rare but can be fatal. We prepared freeze-dried redback spider antivenom for therapeutic use against bites in Japan by immunization of horse plasma. This study included...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Japanese Society of Toxicologic Pathology
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938211/ https://www.ncbi.nlm.nih.gov/pubmed/29749999 http://dx.doi.org/10.1293/tox.2017-0053 |
_version_ | 1783320741404475392 |
---|---|
author | Yamamoto, Akihiko Harano, Satomi Shinya, Noriko Nagano, Ayataka Miyatsu, Yoshinobu Sawabe, Kyouko Matsumura, Takayuki Ato, Manabu Takahashi, Motohide Taki, Hisashi Hifumi, Toru |
author_facet | Yamamoto, Akihiko Harano, Satomi Shinya, Noriko Nagano, Ayataka Miyatsu, Yoshinobu Sawabe, Kyouko Matsumura, Takayuki Ato, Manabu Takahashi, Motohide Taki, Hisashi Hifumi, Toru |
author_sort | Yamamoto, Akihiko |
collection | PubMed |
description | The redback spider (Latrodectus hasseltii) is nonindigenous to Japan but has now spread throughout the country. Bites to humans are rare but can be fatal. We prepared freeze-dried redback spider antivenom for therapeutic use against bites in Japan by immunization of horse plasma. This study included two nonclinical tests of the antivenom: a local irritation study involving a single intramuscular administration to rabbits (with injections of physiological saline and an existing freeze-dried diphtheria antitoxin as control and comparison substances, respectively) and a 2-week repeated intermittent intravenous-dose toxicity study in rats. The irritation study showed the antivenom’s irritancy to be comparable with that of the saline and the existing antitoxin preparations under the test conditions. In a repeated-dose toxicity study, no toxicity change was found in male or female rats, and the no-observed-adverse-effect level (NOAEL) was judged to be a dose volume of 20 mL/kg (1082 units/kg antivenom activity) in both male and female rats. In addition, there was no toxicological difference between proteinaceous diphtheria antitoxin and redback spider antivenom prepared to have the same protein content and the same additive composition. Based on these findings, we will further advance our research towards clinical application of the redback spider antivenom. This research was supported by the Research Program on Emerging and Re-emerging Infectious Disease of the Japan Agency for Medical Research and Development. |
format | Online Article Text |
id | pubmed-5938211 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Japanese Society of Toxicologic Pathology |
record_format | MEDLINE/PubMed |
spelling | pubmed-59382112018-05-10 Freeze-dried equine-derived redback spider antivenom: a local irritation study by intramuscular injection in rabbits and a repeated-dose toxicity study in rats Yamamoto, Akihiko Harano, Satomi Shinya, Noriko Nagano, Ayataka Miyatsu, Yoshinobu Sawabe, Kyouko Matsumura, Takayuki Ato, Manabu Takahashi, Motohide Taki, Hisashi Hifumi, Toru J Toxicol Pathol Original Article The redback spider (Latrodectus hasseltii) is nonindigenous to Japan but has now spread throughout the country. Bites to humans are rare but can be fatal. We prepared freeze-dried redback spider antivenom for therapeutic use against bites in Japan by immunization of horse plasma. This study included two nonclinical tests of the antivenom: a local irritation study involving a single intramuscular administration to rabbits (with injections of physiological saline and an existing freeze-dried diphtheria antitoxin as control and comparison substances, respectively) and a 2-week repeated intermittent intravenous-dose toxicity study in rats. The irritation study showed the antivenom’s irritancy to be comparable with that of the saline and the existing antitoxin preparations under the test conditions. In a repeated-dose toxicity study, no toxicity change was found in male or female rats, and the no-observed-adverse-effect level (NOAEL) was judged to be a dose volume of 20 mL/kg (1082 units/kg antivenom activity) in both male and female rats. In addition, there was no toxicological difference between proteinaceous diphtheria antitoxin and redback spider antivenom prepared to have the same protein content and the same additive composition. Based on these findings, we will further advance our research towards clinical application of the redback spider antivenom. This research was supported by the Research Program on Emerging and Re-emerging Infectious Disease of the Japan Agency for Medical Research and Development. Japanese Society of Toxicologic Pathology 2018-02-19 2018-04 /pmc/articles/PMC5938211/ /pubmed/29749999 http://dx.doi.org/10.1293/tox.2017-0053 Text en ©2018 The Japanese Society of Toxicologic Pathology This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Yamamoto, Akihiko Harano, Satomi Shinya, Noriko Nagano, Ayataka Miyatsu, Yoshinobu Sawabe, Kyouko Matsumura, Takayuki Ato, Manabu Takahashi, Motohide Taki, Hisashi Hifumi, Toru Freeze-dried equine-derived redback spider antivenom: a local irritation study by intramuscular injection in rabbits and a repeated-dose toxicity study in rats |
title | Freeze-dried equine-derived redback spider antivenom: a local irritation
study by intramuscular injection in rabbits and a repeated-dose toxicity study in
rats |
title_full | Freeze-dried equine-derived redback spider antivenom: a local irritation
study by intramuscular injection in rabbits and a repeated-dose toxicity study in
rats |
title_fullStr | Freeze-dried equine-derived redback spider antivenom: a local irritation
study by intramuscular injection in rabbits and a repeated-dose toxicity study in
rats |
title_full_unstemmed | Freeze-dried equine-derived redback spider antivenom: a local irritation
study by intramuscular injection in rabbits and a repeated-dose toxicity study in
rats |
title_short | Freeze-dried equine-derived redback spider antivenom: a local irritation
study by intramuscular injection in rabbits and a repeated-dose toxicity study in
rats |
title_sort | freeze-dried equine-derived redback spider antivenom: a local irritation
study by intramuscular injection in rabbits and a repeated-dose toxicity study in
rats |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938211/ https://www.ncbi.nlm.nih.gov/pubmed/29749999 http://dx.doi.org/10.1293/tox.2017-0053 |
work_keys_str_mv | AT yamamotoakihiko freezedriedequinederivedredbackspiderantivenomalocalirritationstudybyintramuscularinjectioninrabbitsandarepeateddosetoxicitystudyinrats AT haranosatomi freezedriedequinederivedredbackspiderantivenomalocalirritationstudybyintramuscularinjectioninrabbitsandarepeateddosetoxicitystudyinrats AT shinyanoriko freezedriedequinederivedredbackspiderantivenomalocalirritationstudybyintramuscularinjectioninrabbitsandarepeateddosetoxicitystudyinrats AT naganoayataka freezedriedequinederivedredbackspiderantivenomalocalirritationstudybyintramuscularinjectioninrabbitsandarepeateddosetoxicitystudyinrats AT miyatsuyoshinobu freezedriedequinederivedredbackspiderantivenomalocalirritationstudybyintramuscularinjectioninrabbitsandarepeateddosetoxicitystudyinrats AT sawabekyouko freezedriedequinederivedredbackspiderantivenomalocalirritationstudybyintramuscularinjectioninrabbitsandarepeateddosetoxicitystudyinrats AT matsumuratakayuki freezedriedequinederivedredbackspiderantivenomalocalirritationstudybyintramuscularinjectioninrabbitsandarepeateddosetoxicitystudyinrats AT atomanabu freezedriedequinederivedredbackspiderantivenomalocalirritationstudybyintramuscularinjectioninrabbitsandarepeateddosetoxicitystudyinrats AT takahashimotohide freezedriedequinederivedredbackspiderantivenomalocalirritationstudybyintramuscularinjectioninrabbitsandarepeateddosetoxicitystudyinrats AT takihisashi freezedriedequinederivedredbackspiderantivenomalocalirritationstudybyintramuscularinjectioninrabbitsandarepeateddosetoxicitystudyinrats AT hifumitoru freezedriedequinederivedredbackspiderantivenomalocalirritationstudybyintramuscularinjectioninrabbitsandarepeateddosetoxicitystudyinrats |