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Investigation of genotoxic effects of doripenem using cytogenetic and molecular methods

M Aydin1, E Rencüzoğullari1, O Bozkurt2

  • 1Departmant of Biology, Faculty of Science and Letters, Adiyaman University, Adiyaman, Turkey.

Cellular and Molecular Biology (Noisy-Le-Grand, France)
|November 4, 2017
PubMed

Insights

Doripenem (DRP) showed no genotoxic effects in human lymphocytes via cytogenetic tests. However, molecular analysis indicated potential genomic instability at higher concentrations and longer exposure, suggesting careful consideration of therapeutic doses.

Area of Science:

  • Pharmacology
  • Genetics
  • Toxicology

Background:

  • Doripenem (DRP) is a broad-spectrum antibiotic.
  • Limited data exists on the genotoxic effects of DRP.
  • Assessing DRP's genotoxicity is crucial for its clinical safety profile.

Purpose of the Study:

  • To investigate the genotoxic effects of doripenem (DRP) in human peripheral lymphocytes.
  • To evaluate DRP's potential to induce DNA damage using cytogenetic and molecular methods.
  • To determine the safety of DRP concerning genotoxicity at various concentrations and exposure times.

Main Methods:

  • Human peripheral lymphocytes were exposed to DRP (100, 200, 400 μg/ml) for 24 and 48 hours.
  • Cytogenetic analysis included chromosome aberration (CA) and micronucleus (MN) assays.
  • Molecular analysis utilized the random amplified polymorphic DNA (RAPD-PCR) technique to assess genomic template stability.

Main Results:

  • DRP did not induce chromosome aberrations or micronucleus formation at any tested concentration or duration.
  • No cytotoxic effects were observed.
  • DRP increased polymorphic band numbers and decreased genomic template stability, particularly after 48 hours of exposure.

Conclusions:

  • Doripenem (DRP) demonstrates a lack of genotoxic risk at therapeutic doses based on cytogenetic assays.
  • Molecular analysis suggests potential for genomic instability with prolonged exposure, warranting further investigation.
  • DRP appears to be a reliable antibiotic, likely due to its rapid metabolism.
Keywords:
Chromosome aberrationDoripenem.GenotoxicityMicronucleusRAPD-PCR

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