Cyclosporin A and tacrolimus are powerful immunosuppressants used as post-operation medication after allogenic transplantations. Unfortunately, the drugs Sandimmune (cyclosporin A) and Prograf (tacrolimus) exhibit negative side effects. These side effects may be linked not only to the active ingredients themselves, but also to the vehicle used for their delivery – Cremophor EL and/or ethanol. Sandimmune, Prograf, ethanol, Cremophor EL or Cremophor EL with ethanol (i.e. the complete vehicle) in a saline solution were administered to male Wistar rats either on 6th and 7th or 30th and 31st day postnatally. The functional changes in the nervous system elicited by these substances were assessed by observing the intensity of seizures induced by a single i.p. injection of pilocarpine at 60th postnatal day. Brain anatomy was also analyzed by comparing brain mass, lateral ventricle relative area, thickness of cerebral hemisphere wall, relative size of the hippocampus as well as total density of cresyl violet-stained neurons in the cerebral hemisphere walls between control and experimental animals. Our data point to a significant effect of all tested substances on central nervous system development. The greatest effects on seizure severity and brain structure were associated with the complete vehicle. Such effects (although less sever) were also observed for Cremophor EL and ethanol given separately.
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