TY - JOUR
T1 - Cobinamide is effective for treatment of hydrogen sulfide-induced neurological sequelae in a mouse model
AU - Anantharam, Poojya
AU - Whitley, Elizabeth M.
AU - Mahama, Belinda
AU - Kim, Dong Suk
AU - Sarkar, Souvarish
AU - Santana, Cristina
AU - Chan, Adriano
AU - Kanthasamy, Anumantha G.
AU - Kanthasamy, Arthi
AU - Boss, Gerry R.
AU - Rumbeiha, Wilson K.
N1 - Publisher Copyright:
© 2017 New York Academy of Sciences.
PY - 2017
Y1 - 2017
N2 - Hydrogen sulfide (H2S) is a highly neurotoxic gas. Acute exposure can lead to neurological sequelae among survivors. A drug for treating neurological sequelae in survivors of acute H2S 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 H2S. 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 H2S exposure. For objective 2, mice were injected intramuscularly with 100 mg/kg Cob at 2, 15, and 30 min after H2S exposure. For both objectives, mice were exposed to 765 ppm of H2S gas. Cob significantly reduced H2S-induced lethality in a dose-dependent manner (P < 0.05). Cob-treated mice exhibited significantly fewer seizures and knockdowns compared with theH2S-exposed group.Cob also reversedH2S-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 H2S-induced neurological sequelae.
AB - Hydrogen sulfide (H2S) is a highly neurotoxic gas. Acute exposure can lead to neurological sequelae among survivors. A drug for treating neurological sequelae in survivors of acute H2S 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 H2S. 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 H2S exposure. For objective 2, mice were injected intramuscularly with 100 mg/kg Cob at 2, 15, and 30 min after H2S exposure. For both objectives, mice were exposed to 765 ppm of H2S gas. Cob significantly reduced H2S-induced lethality in a dose-dependent manner (P < 0.05). Cob-treated mice exhibited significantly fewer seizures and knockdowns compared with theH2S-exposed group.Cob also reversedH2S-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 H2S-induced neurological sequelae.
KW - Cobinamide
KW - Hydrogen sulfide
KW - Neurological sequelae
KW - Neuroprotection
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U2 - 10.1111/nyas.13559
DO - 10.1111/nyas.13559
M3 - Article
C2 - 29239480
AN - SCOPUS:85039561783
SN - 0077-8923
VL - 1408
SP - 61
EP - 78
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
IS - 1
ER -