Toxicity of corticosteroids and catecholamines for mice neuronal cell cultures: Role of preservatives

Abstract

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 μM. 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 μM and sodium metabisulfite at 10 and 100 μM. Neuronal death was significantly increased by dopamine, Revivan, dobutamine, Dobutrex, and sulfites at 10 and 100 μM 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.

Keywords:

• Corticosteroids
• catecholamines
• sulfites
• neurotoxicity
• preterm infants