Induction of apoptosis in mouse brain capillary endothelial cells by cyclosporin A and tacrolimus.
Although cyclosporin A and tacrolimus are used clinically as potent immunosuppressants, there have been reports of neurotoxicity and encephalopathy. A possible mechanism is that these drugs damage the blood-brain barrier (BBB), inducing dysfunction and increased permeability, and are then able to enter the brain. We studied the cytotoxicity of cyclosporin A and tacrolimus, focused on apoptosis induction, using an immortalized cell line established from BALB/c mouse cerebral microvessel endothelial cells (MBEC4). We found that these two drugs induced cell shrinkage, chromatin condensation and DNA fragmentation, which are characteristics of apoptosis. Our data suggest that the induction of apoptosis on the brain capillary endothelial cells may be at least partly involved in the occurrence of immunosuppressant-induced encephalopathy.
Kochi
S
S
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Takanaga
H
H
Matsuo
H
H
Ohtani
H
H
Naito
M
M
Tsuruo
T
T
Sawada
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002196:Capillaries / Q000166:cytology / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D004247:DNA; D016559:Tacrolimus