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Cobinamide is effective for treatment of hydrogen sulfide–induced neurological sequelae in a mouse model
Author(s) -
Anantharam Poojya,
Whitley Elizabeth M.,
Mahama Belinda,
Kim DongSuk,
Sarkar Souvarish,
Santana Cristina,
Chan Adriano,
Kanthasamy Anumantha G.,
Kanthasamy Arthi,
Boss Gerry R.,
Rumbeiha Wilson K.
Publication year - 2017
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.13559
Subject(s) - neuroprotection , neurochemical , medicine , cytochrome c oxidase , neurodegeneration , pharmacology , anesthesia , enzyme , chemistry , biochemistry , disease
Hydrogen sulfide (H 2 S) is a highly neurotoxic gas. Acute exposure can lead to neurological sequelae among survivors. A drug for treating neurological sequelae in survivors of acute H 2 S intoxication is needed. Using a novel mouse model we evaluated the efficacy of cobinamide (Cob) for increasing survival of, and reducing neurological sequalae in, mice exposed to sublethal doses of H 2 S. There were two objectives: (1) to determine the dose–response efficacy of Cob and (2) to determine the effective therapeutic time window of Cob. To explore objective 1, mice were injected intramuscularly with Cob at 0, 50, or 100 mg/kg at 2 min after H 2 S exposure. For objective 2, mice were injected intramuscularly with 100 mg/kg Cob at 2, 15, and 30 min after H 2 S exposure. For both objectives, mice were exposed to 765 ppm of H 2 S gas. Cob significantly reduced H 2 S‐induced lethality in a dose‐dependent manner ( P < 0.05). Cob‐treated mice exhibited significantly fewer seizures and knockdowns compared with the H 2 S‐exposed group. Cob also reversed H 2 S‐induced weight loss, behavioral deficits, neurochemical changes, cytochrome c oxidase enzyme inhibition, and neurodegeneration in a dose‐ and time‐dependent manner ( P < 0.01). Overall, these findings show that Cob increases survival and is neuroprotective in a mouse model of H 2 S‐induced neurological sequelae.