• Philippe Haouzi, Marissa McCann, JuFang Wang, Xue-Qian Zhang, Jianliang Song, Ilker Sariyer, Diane Langford, Maryline Santerre, Nicole Tubbs, Annick Haouzi-Judenherc, and Joseph Y Cheung.
• Division of Pulmonary and Critical Care Medicine, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania.
• Ann. N. Y. Acad. Sci. 2020 Nov 1; 1479 (1): 108-121.

AbstractThe aim of the present study was to determine whether methylene blue (MB) could directly oppose the neurological toxicity of a lethal cyanide (CN) intoxication. KCN, infused at the rate of 0.375 mg/kg/min intravenously, produced 100% lethality within 15 min in unanaesthetized rats (n = 12). MB at 10 (n = 5) or 20 mg/kg (n = 5), administered 3 min into CN infusion, allowed all animals to survive with no sequelae. No apnea and gasping were observed at 20 mg/kg MB (P < 0.001). The onset of coma was also significantly delayed and recovery from coma was shortened in a dose-dependent manner (median of 359 and 737 seconds, respectively, at 20 and 10 mg/kg). At 4 mg/kg MB (n = 5), all animals presented faster onset of coma and apnea and a longer period of recovery than at the highest doses (median 1344 seconds, P < 0.001). MB reversed NaCN-induced resting membrane potential depolarization and action potential depression in primary cultures of human fetal neurons intoxicated with CN. MB restored calcium homeostasis in the CN-intoxicated human SH-SY5Y neuroblastoma cell line. We conclude that MB mitigates the neuronal toxicity of CN in a dose-dependent manner, preventing the lethal depression of respiratory medullary neurons and fatal outcome.© 2020 New York Academy of Sciences.

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