In vitro toxic effects of certain antibiotics on the fibroblasts of two children with I-cell disease.
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.
Dumontel
C
C
Latoratoire d'Histologie et Embryologie moléculaires, Faculté de médecine Laënnec, Lyon, France.
Constant
H
H
Souillet
G
G
Zabot
M T
MT
D000900:Anti-Bacterial Agents / Q000633:toxicity*; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D002675:Child, Preschool; D002784:Cholesterol / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D009081:Mucolipidoses / Q000473:pathology* / Q000628:therapy; D012867:Skin / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism
D000900:Anti-Bacterial Agents; D002784:Cholesterol; D013108:Sphingomyelin Phosphodiesterase