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Updated: Jan 3, 2026

Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice
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Elucidating the time-dependent changes in the urinary metabolome under doxorubicin-induced nephrotoxicity

Aiping Li1, Wangning Zhang1, Lichao Zhang2

  • 1Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, Shanxi, China.

Toxicology Letters
|November 25, 2019
PubMed

Insights

Doxorubicin causes kidney damage, and this study identifies the 14th day as critical for modeling this nephrotoxicity. Metabolomics revealed key metabolic pathways involved in doxorubicin-induced renal toxicity.

Area of Science:

  • Biochemistry
  • Toxicology
  • Metabolomics

Background:

  • Doxorubicin is a known cardiotoxic and nephrotoxic drug, frequently used as a model compound.
  • Systematic investigation of time-dependent metabolic changes in doxorubicin-induced nephrotoxicity is limited.

Purpose of the Study:

  • To assess time-dependent alterations in doxorubicin-induced nephropathy using urinary metabolomics.
  • To elucidate the molecular mechanisms underlying doxorubicin-induced renal toxicity.

Main Methods:

  • Urinary metabolomics was employed to analyze time-dependent changes.
  • Pathway analysis identified key metabolic pathways.
  • Partial least squares regression analysis (PLS-RA) and molecular docking were used for validation.

Main Results:

  • The 14th day was identified as a critical time point for constructing the nephropathy model.
  • Five pathways were found to be significantly altered (impact >0.1, FDR <0.1, p <0.05).
  • Butanoate metabolism, alanine/aspartate/glutamate metabolism, and arginine/proline metabolism were highlighted and validated.

Conclusions:

  • Urinary metabolomics combined with PLS-RA and molecular docking effectively elucidates time-dependent doxorubicin toxicity mechanisms.
  • This study provides a foundation for developing accurate nephropathy models.
  • The findings offer insights into the molecular basis of doxorubicin-induced kidney damage.
Keywords:
DoxorubicinMetabolomicsMolecular dockingNephrotoxicityPLS-RATime-dependent changes

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