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Updated: Oct 12, 2025

Cell Type-specific Gene Expression Profiling in the Mouse Liver
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Investigation of Ifosfamide Toxicity Induces Common Upstream Regulator in Liver and Kidney

Hyoung-Yun Han1,2, Mi-Sun Choi1,3, Seokjoo Yoon1,2

  • 1Department of Predictive Toxicology, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Korea.

International Journal of Molecular Sciences
|November 27, 2021
PubMed

Insights

Ifosfamide causes severe kidney toxicity in rats after repeated doses, affecting cholesterol and kidney failure genes. Interferon regulatory factor 7 is a key regulator identified in liver and kidney tissues.

Area of Science:

  • Toxicology
  • Pharmacology
  • Genomics

Background:

  • Ifosfamide is a chemotherapy drug used for solid cancers.
  • Understanding its toxicity is crucial for patient safety.

Purpose of the Study:

  • To evaluate the toxicity of ifosfamide in rats.
  • To identify molecular mechanisms of ifosfamide-induced toxicity using toxicogenomics.

Main Methods:

  • Single and multiple dose intraperitoneal administration of ifosfamide in rats.
  • Good Laboratory Practice (GLP) guidelines.
  • Microarray analysis and real-time RT-PCR.

Main Results:

  • Single ifosfamide dose (50 mg/kg) showed no toxicity.
  • Repeated doses caused severe renal toxicity, with elevated blood urea nitrogen and creatinine.
  • Gene expression analysis revealed affected cholesterol synthesis genes in the liver and renal failure genes in the kidney.
  • Interferon regulatory factor 7 was identified as a key upstream regulator in both organs.

Conclusions:

  • Ifosfamide exhibits kidney-biased toxicity.
  • Identical gene expression alterations were observed in the liver and kidney.
  • Further toxicogenomic studies are needed to clarify gene-toxicity relationships.
Keywords:
hepatotoxicityifosfamideintraperitoneal toxicitynephrotoxicity

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