Cobinamide is effective for treatment of hydrogen sulfide-induced neurological sequelae in a mouse model

Poojya Anantharam, Elizabeth M. Whitley, Belinda Mahama, Dong Suk Kim, Souvarish Sarkar, Cristina Santana, Adriano Chan, Anumantha G. Kanthasamy, Arthi Kanthasamy, Gerry R. Boss, Wilson K. Rumbeiha

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)61-78
Number of pages18
JournalAnnals of the New York Academy of Sciences
Volume1408
Issue number1
DOIs
StatePublished - 2017

Keywords

  • Cobinamide
  • Hydrogen sulfide
  • Neurological sequelae
  • Neuroprotection

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • History and Philosophy of Science

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