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The vitamin B12 analog cobinamide is an effective hydrogen sulfide antidote in a lethal rabbit model.
Clin Toxicol (Phila) 2014; 52(5):490-7CT

Abstract

BACKGROUND AND PURPOSE

Hydrogen sulfide (H2S) is a highly toxic gas for which no effective antidotes exist. It acts, at least in part, by binding to cytochrome c oxidase, causing cellular asphyxiation and anoxia. We investigated the effects of three different ligand forms of cobinamide, a vitamin B12 analog, to reverse sulfide (NaHS) toxicity.

METHODS

New Zealand white rabbits received a continuous intravenous (IV) infusion of NaHS (3 mg/min) until expiration or a maximum 270 mg dose. Animals received six different treatments, administered at the time when they developed signs of severe toxicity: Group 1-saline (placebo group, N = 9); Group 2--IV hydroxocobalamin (N = 7); Group 3--IV aquohydroxocobinamide (N = 6); Group 4--IV sulfitocobinamide (N = 6); Group 5--intramuscular (IM) sulfitocobinamide (N = 6); and Group 6-IM dinitrocobinamide (N = 8). Blood was sampled intermittently, and systemic blood pressure and deoxygenated and oxygenated hemoglobin were measured continuously in peripheral muscle and over the brain region; the latter were measured by diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS).

RESULTS

Compared with the saline controls, all cobinamide derivatives significantly increased survival time and the amount of NaHS that was tolerated. Aquohydroxocobinamide was most effective (261.5 ± 2.4 mg NaHS tolerated vs. 93.8 ± 6.2 mg in controls, p < 0.0001). Dinitrocobinamide was more effective than sulfitocobinamide. Hydroxocobalamin was not significantly more effective than the saline control.

CONCLUSIONS

Cobinamide is an effective agent for inhibiting lethal sulfide exposure in this rabbit model. Further studies are needed to determine the optimal dose and form of cobinamide and route of administration.

Authors+Show Affiliations

Beckman Laser Institute, University of California , Irvine, CA , USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

24716792

Citation

Brenner, M, et al. "The Vitamin B12 Analog Cobinamide Is an Effective Hydrogen Sulfide Antidote in a Lethal Rabbit Model." Clinical Toxicology (Philadelphia, Pa.), vol. 52, no. 5, 2014, pp. 490-7.
Brenner M, Benavides S, Mahon SB, et al. The vitamin B12 analog cobinamide is an effective hydrogen sulfide antidote in a lethal rabbit model. Clin Toxicol (Phila). 2014;52(5):490-7.
Brenner, M., Benavides, S., Mahon, S. B., Lee, J., Yoon, D., Mukai, D., ... Boss, G. R. (2014). The vitamin B12 analog cobinamide is an effective hydrogen sulfide antidote in a lethal rabbit model. Clinical Toxicology (Philadelphia, Pa.), 52(5), pp. 490-7. doi:10.3109/15563650.2014.904045.
Brenner M, et al. The Vitamin B12 Analog Cobinamide Is an Effective Hydrogen Sulfide Antidote in a Lethal Rabbit Model. Clin Toxicol (Phila). 2014;52(5):490-7. PubMed PMID: 24716792.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The vitamin B12 analog cobinamide is an effective hydrogen sulfide antidote in a lethal rabbit model. AU - Brenner,M, AU - Benavides,S, AU - Mahon,S B, AU - Lee,J, AU - Yoon,D, AU - Mukai,D, AU - Viseroi,M, AU - Chan,A, AU - Jiang,J, AU - Narula,N, AU - Azer,S M, AU - Alexander,C, AU - Boss,G R, Y1 - 2014/04/09/ PY - 2014/4/11/entrez PY - 2014/4/11/pubmed PY - 2014/8/7/medline KW - CNS/Psychological KW - Heart KW - Lung KW - Muscle SP - 490 EP - 7 JF - Clinical toxicology (Philadelphia, Pa.) JO - Clin Toxicol (Phila) VL - 52 IS - 5 N2 - BACKGROUND AND PURPOSE: Hydrogen sulfide (H2S) is a highly toxic gas for which no effective antidotes exist. It acts, at least in part, by binding to cytochrome c oxidase, causing cellular asphyxiation and anoxia. We investigated the effects of three different ligand forms of cobinamide, a vitamin B12 analog, to reverse sulfide (NaHS) toxicity. METHODS: New Zealand white rabbits received a continuous intravenous (IV) infusion of NaHS (3 mg/min) until expiration or a maximum 270 mg dose. Animals received six different treatments, administered at the time when they developed signs of severe toxicity: Group 1-saline (placebo group, N = 9); Group 2--IV hydroxocobalamin (N = 7); Group 3--IV aquohydroxocobinamide (N = 6); Group 4--IV sulfitocobinamide (N = 6); Group 5--intramuscular (IM) sulfitocobinamide (N = 6); and Group 6-IM dinitrocobinamide (N = 8). Blood was sampled intermittently, and systemic blood pressure and deoxygenated and oxygenated hemoglobin were measured continuously in peripheral muscle and over the brain region; the latter were measured by diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS). RESULTS: Compared with the saline controls, all cobinamide derivatives significantly increased survival time and the amount of NaHS that was tolerated. Aquohydroxocobinamide was most effective (261.5 ± 2.4 mg NaHS tolerated vs. 93.8 ± 6.2 mg in controls, p < 0.0001). Dinitrocobinamide was more effective than sulfitocobinamide. Hydroxocobalamin was not significantly more effective than the saline control. CONCLUSIONS: Cobinamide is an effective agent for inhibiting lethal sulfide exposure in this rabbit model. Further studies are needed to determine the optimal dose and form of cobinamide and route of administration. SN - 1556-9519 UR - https://www.unboundmedicine.com/medline/citation/24716792/The_vitamin_B12_analog_cobinamide_is_an_effective_hydrogen_sulfide_antidote_in_a_lethal_rabbit_model_ L2 - http://www.tandfonline.com/doi/full/10.3109/15563650.2014.904045 DB - PRIME DP - Unbound Medicine ER -