Inhibition of calcineurin activity and protection against cyclosporine A induced cytotoxicity by prednisolone sodium succinate in human peripheral mononuclear cells.
We have investigated the effects of prednisolone sodium succinate (Pss) and cyclosporin A (CSA), applied alone or concurrently, on the release of arachidonic acid (AA) (cytosolic phospholipase A(2) (cPLA(2)) activity) and on the calcineurin (CN) activity of human peripheral blood mononuclear cells (PBMC). The cytotoxic damage to the cells treated by the drugs was estimated by the release of lactate dehydrogenase (LDH). We found that Pss (10(-5) M) could inhibit the CN activity and higher concentrations (10(-4) M) could decrease the cytotoxic damage caused by CSA (10(-4) M) during their combined application. CSA had no specific effect on the release of AA from the cells. In the combined clinical use of glucocorticosteroids (GCS) and CSA, their additive inhibitory effect on CN activity and the protective membrane influence of GCS against the cytotoxicity of CSA may be beneficial.
Sipka
S
S
3rd Department of Internal Medicine, University Medical School of Debrecen, Móricz Zs. út 22, H-4004, Debrecen, Hungary. sipka@iiibel.dote.hu
Szücs
K
K
Szántó
S
S
Kovács
I
I
Lakos
G
G
Antal-Szalmás
P
P
Szegedi
G
G
Gergely
P
P
D000328:Adult; D016718:Arachidonic Acid / Q000032:analysis; D065095:Calcineurin Inhibitors; D002462:Cell Membrane / Q000187:drug effects; D016572:Cyclosporine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D011239:Prednisolone / Q000031:analogs & derivatives / Q000494:pharmacology*
D065095:Calcineurin Inhibitors; D016718:Arachidonic Acid; D016572:Cyclosporine; D011239:Prednisolone; D007770:L-Lactate Dehydrogenase; D010741:Phospholipases A; C021322:prednisolone hemisuccinate