Toxicity of corticosteroids and catecholamines for mice neuronal cell cultures: Role of preservatives.
OBJECTIVE
To confirm previous reports on dexamethasone and sulfite neurotoxicity, and to investigate methylprednisolone, dopamine, and dobutamine neurotoxicity.


METHODS
Pure dexamethasone, injectable dexamethasone containing sodium metabisulfite (Soludecadron), pure methylprednisolone, injectable methylprednisolone (Solu-Medrol), pure dopamine, injectable dopamine containing potassium metabisulfite (Revivan), pure dobutamine, injectable dobutamine containing sodium metabisulfite (Dobutrex), and sodium metabisulfite were added to the medium of mixed glial-neuronal cell cultures at concentrations of 0.1, 1, 10, and 100 microM. Cell damage induced by glucocorticoids was assessed by measuring the release of lactate dehydrogenase (LDH) from the injured cells into the extracellular fluid during the 24 hours of exposure to drugs. Cell damage induced by catecholamines was assessed using the fluorescent dye propidium iodide (PI) method 24 hours after exposure to the drugs.


RESULTS
Methylprednisolone and Solu-Medrol did not affect neuronal death, which was increased by dexamethasone and Soludecadron at 100 microM and sodium metabisulfite at 10 and 100 microM. Neuronal death was significantly increased by dopamine, Revivan, dobutamine, Dobutrex, and sulfites at 10 and 100 microM concentrations.


CONCLUSIONS
In vitro dexamethasone, Soludecadron, and sulfites increase neuronal cell death, while methylprednisolone and Solu-Medrol are not neurotoxic; dopamine and dobutamine were found neurotoxic independently from sulfite toxicity.
Dani
Carlo
C
Department of Surgical and Medical Critical Care, Section of Neonatology, Careggi University Hospital of Florence. Florence, Italy. cdani@unifi.it
Vestri
Valentina
V
Bertini
Giovanna
G
Pratesi
Simone
S
Rubaltelli
Firmino F
FF
D000818:Animals; D000831:Animals, Newborn; D002395:Catecholamines / Q000008:administration & dosage / Q000633:toxicity*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000008:administration & dosage / Q000633:toxicity; D004298:Dopamine / Q000008:administration & dosage / Q000633:toxicity; D005938:Glucocorticoids / Q000008:administration & dosage / Q000633:toxicity*; D008775:Methylprednisolone / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D011310:Preservatives, Pharmaceutical / Q000008:administration & dosage / Q000633:toxicity; D013447:Sulfites / Q000008:administration & dosage / Q000633:toxicity
D002395:Catecholamines; D005938:Glucocorticoids; D011310:Preservatives, Pharmaceutical; D013447:Sulfites; C005200:sodium metabisulfite; D003907:Dexamethasone; D004298:Dopamine; D008775:Methylprednisolone