Reactive blue prevented caffeine-induced neurotoxicity by an independent mechanism from intracellular calcium currents in cell culture from auditory cortex of rats.

Neurotoxicity induced by caffeine in auditory-neuron cultures was studied in rat pups. For possible protective effect, reactive blue (RB) alone and in combination with dantrolene were tested in subsequent doses. RB was found to have a U-shape neuroprotective effect in caffeine neurotoxicity. Dantrolene was also tested in combined application in caffeine neurotoxicity. Despite the existing neuroprotection, no additional protection was obtained with various doses of dantrolene. In conclusion, RB may exert neuroprotective effect by increasing intracellular ATP levels in caffeine toxicity. High ATP levels may postpone the toxic cascade. Dantrolene as an endoplasmic reticulum calcium release blocker had no additional protective effect, suggesting that the increased intracellular calcium levels may be involved in later states of the toxic cascade, occurring after the compensatory phase of the cell death.