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Antidotal effects of methylene blue against cyanide neurological toxicity: in vivo and in vitro studies
Author(s) -
Haouzi Philippe,
McCann Marissa,
Wang JuFang,
Zhang XueQian,
Song Jianliang,
Sariyer Ilker,
Langford Diane,
Santerre Maryline,
Tubbs Nicole,
HaouziJudenherc Annick,
Cheung Joseph Y.
Publication year - 2020
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.14353
Subject(s) - toxicity , coma (optics) , methylene blue , in vivo , cyanide , chemistry , antidote , anesthesia , pharmacology , apnea , medicine , biology , biochemistry , inorganic chemistry , optics , catalysis , physics , microbiology and biotechnology , photocatalysis
The 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.