Genome-wide gene expression analysis reveals molecular insights into the drug-induced toxicity of nephrotoxic agents.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE
    • Publication Information:
      Publication: <2008->: Amsterdam : Elsevier
      Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
    • Subject Terms:
      Colistin*/adverse effects ; Ifosfamide*/adverse effects ; Ifosfamide*/metabolism; Animals ; Gene Expression ; Indomethacin/pharmacology ; Kidney/metabolism ; Puromycin/metabolism ; Puromycin/toxicity ; Rats
    • Abstract:
      Drug-induced nephrotoxicity is frequently reported. However, the mechanisms underlying nephrotoxic medications and their overlapping molecular events, which might have therapeutic value, are unclear. We performed a genome-wide analysis of gene expression and a gene set enrichment analysis to identify common and unique pathways associated with the toxicity of colistin, ifosfamide, indomethacin, and puromycin. Rats were randomly allocated into the treatment or control group. The treatment group received a toxic dose once daily of each investigated drug for 1 week. Differentially expressed genes were found in the drug-treated kidney and liver compared to the control, except for colistin in the liver. Upregulated pathways were mainly related to cell death, cell cycle, protein synthesis, and immune response modulation in the kidney. Cell cycle was upregulated by all drugs. Downregulated pathways were associated with carbon metabolism, amino acid metabolism, and fatty acid metabolism. Indomethacin, colistin, and puromycin shared the most altered pathways in the kidney. Ifosfamide and indomethacin affected molecular processes greatly in the liver. Our findings provide insight into the mechanisms underlying the renal and hepatic adverse effects of the four drugs. Further investigation should explore the combinatory drug therapies that attenuate the toxic effects and maximize the effectiveness of nephrotoxic drugs.
      (Copyright © 2022. Published by Elsevier Inc.)
    • Contributed Indexing:
      Keywords: Colistin; Drug-induced toxicity; Ifosfamide; Indomethacin; Puromycin; Transcriptomics
    • Accession Number:
      4A6ZS6Q2CL (Puromycin)
      UM20QQM95Y (Ifosfamide)
      XXE1CET956 (Indomethacin)
      Z67X93HJG1 (Colistin)
    • Publication Date:
      Date Created: 20220719 Date Completed: 20220823 Latest Revision: 20220823
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.lfs.2022.120801
    • Accession Number:
      35850247