In vitro toxic effects of certain antibiotics on the fibroblasts of two children with I-cell disease

Cell Biol Toxicol. 1998 Oct;14(5):333-43. doi: 10.1023/a:1007533723782.

Abstract

Six antibiotics, pefloxacin (Peflacine), fosfomycin (Fosfocine), teicoplanin (Targocid), vancomycin (Vancocine), ceftazidime (Fortum), piperacillin (Piperilline), that may be used as a systematic coverage during bone marrow transplantation have been tested on dermal fibroblasts of one control subject and two I-cell disease patients, along with five subcultures, corresponding to 5 weeks of culture. The possible toxicity of these molecules was assessed. The evaluation of lysosomal enzyme sphingomyelinase activity, detection of free intracellular cholesterol and the light- and electron-microscopic examination of treated cells were used as measures of metabolic interference and cytotoxicity. Our study shows that despite a lack of any metabolic sign of interference (no modification in enzyme activity, no increase in free intracellular cholesterol), all the antibiotics tested induced a cytotoxic effect which was notably amplified in the I-cell populations. This may be due to the lysosomal lipid storage of these cells which modifies the relationship between the antibiotic and the cell by inducing a different kind of lipid-antibiotic interference.

MeSH terms

  • Anti-Bacterial Agents / toxicity*
  • Bone Marrow Transplantation
  • Cells, Cultured
  • Child, Preschool
  • Cholesterol / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Fibroblasts / ultrastructure
  • Humans
  • Male
  • Microscopy, Electron
  • Mucolipidoses / pathology*
  • Mucolipidoses / therapy
  • Skin / enzymology
  • Skin / pathology
  • Skin / ultrastructure
  • Sphingomyelin Phosphodiesterase / metabolism

Substances

  • Anti-Bacterial Agents
  • Cholesterol
  • Sphingomyelin Phosphodiesterase