Evaluation of drug toxicity profiles based on the phenotypes of ascidian Ciona intestinalis

Yuji Mizotani, Shun Itoh, Kohji Hotta, Etsu Tashiro, Kotaro Oka, Masaya Imoto

Research output: Contribution to journalArticle

Abstract

In vivo toxicity evaluation using model organisms is an important step for the development of new drugs. Here, we report that Ciona intestinalis, a chordate invertebrate, is beneficial to drug toxicity evaluation for the following reasons: rapid embryonic and larval development, resemblance to vertebrates, ease of management, low cost, transparent body, and low risk of ethical issues. The dynamic phenotypic change of Ciona larvae during metamorphosis prompted us to examine the effect of cytotoxic drugs on its development by quantifying six toxicity endpoints: degenerated tail size, ampulla length, rotation of body axis, stomach size, heart rate, and body size. As a result, mitochondrial respiratory inhibitors, tubulin polymerization/depolymerization inhibitors, or DNA/RNA synthesis inhibitors showed distinct toxicity profiles against these six endpoints, but drugs with the same targets showed a similar toxicity profile in Ciona. Our results suggest Ciona is an effective animal model for profiling drug toxicity and exploring the mechanisms of drugs with unknown targets.

Original languageEnglish
Pages (from-to)656-660
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume463
Issue number4
DOIs
Publication statusPublished - 2015 May 8

Fingerprint

Ciona intestinalis
Urochordata
Drug-Related Side Effects and Adverse Reactions
Toxicity
Nucleic Acid Synthesis Inhibitors
Phenotype
Pharmaceutical Preparations
Nonvertebrate Chordata
Tubulin Modulators
Drug Evaluation
Body Size
Ethics
Embryonic Development
Larva
Vertebrates
Tail
Stomach
Depolymerization
Animal Models
Heart Rate

Keywords

  • Ciona intestinalis
  • DNA/RNA synthesis inhibitor
  • Mitochondria respiratory inhibitor
  • Toxicity endpoint
  • Toxicity profile
  • Tubulin polymerization/depolymerization inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

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abstract = "In vivo toxicity evaluation using model organisms is an important step for the development of new drugs. Here, we report that Ciona intestinalis, a chordate invertebrate, is beneficial to drug toxicity evaluation for the following reasons: rapid embryonic and larval development, resemblance to vertebrates, ease of management, low cost, transparent body, and low risk of ethical issues. The dynamic phenotypic change of Ciona larvae during metamorphosis prompted us to examine the effect of cytotoxic drugs on its development by quantifying six toxicity endpoints: degenerated tail size, ampulla length, rotation of body axis, stomach size, heart rate, and body size. As a result, mitochondrial respiratory inhibitors, tubulin polymerization/depolymerization inhibitors, or DNA/RNA synthesis inhibitors showed distinct toxicity profiles against these six endpoints, but drugs with the same targets showed a similar toxicity profile in Ciona. Our results suggest Ciona is an effective animal model for profiling drug toxicity and exploring the mechanisms of drugs with unknown targets.",
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AU - Oka, Kotaro

AU - Imoto, Masaya

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