title: Antagonism of Acute Sulfide Poisoning in Mice by Nitrite Anion without Methemoglobinemia.
abstract: There are currently no FDA-approved antidotes for H2S/sulfide intoxication. Sodium nitrite, if given prophylactically to Swiss Webster mice, was shown to be highly protective against the acute toxic effects of sodium hydrosulfide (∼LD40 dose) with both agents administered by intraperitoneal injections. However, sodium nitrite administered after the toxicant dose did not detectably ameliorate sulfide toxicity in this fast-delivery, single-shot experimental paradigm. Nitrite anion was shown to rapidly produce NO in the bloodstream, as judged by the appearance of EPR signals attributable to nitrosylhemoglobin and methemoglobin, together amounting to less than 5% of the total hemoglobin present. Sulfide-intoxicated mice were neither helped by the supplemental administration of 100% oxygen nor were there any detrimental effects. Compared to cyanide-intoxicated mice, animals surviving sulfide intoxication exhibited very short knockdown times (if any) and full recovery was extremely fast (∼15 min) irrespective of whether sodium nitrite was administered. Behavioral experiments testing the ability of mice to maintain balance on a rotating cylinder showed no motor impairment up to 24 h post sulfide exposure. It is argued that antagonism of sulfide inhibition of cytochrome c oxidase by NO is the crucial antidotal activity of nitrite rather than formation of methemoglobin.
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, The University of Pittsburgh, 100 Technology Drive, Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Cronican
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, The University of Pittsburgh, 100 Technology Drive, Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Frawley
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, The University of Pittsburgh, 100 Technology Drive, Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Humza
authors.initials: H
authors.lastname: Ahmed
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, The University of Pittsburgh, 100 Technology Drive, Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Linda L
authors.initials: LL
authors.lastname: Pearce
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, The University of Pittsburgh, 100 Technology Drive, Pittsburgh, Pennsylvania 15219, United States.
authors.forename: Jim
authors.initials: J
authors.lastname: Peterson
mesh_terms: D000818:Animals; D000838:Anions / Q000737:chemistry; D000931:Antidotes / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D003486:Cyanides / Q000633:toxicity; D004578:Electron Spin Resonance Spectroscopy; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D008706:Methemoglobin / Q000737:chemistry / Q000378:metabolism; D008708:Methemoglobinemia / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018482:Muscle, Skeletal / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D012977:Sodium Nitrite / Q000494:pharmacology*; D013440:Sulfides / Q000633:toxicity*
chemical_list: D000838:Anions; D000931:Antidotes; D003486:Cyanides; D006454:Hemoglobins; D013440:Sulfides; C008657:nitrosyl hemoglobin; D009569:Nitric Oxide; D008706:Methemoglobin; D003576:Electron Transport Complex IV; C025451:sodium bisulfide; D012977:Sodium Nitrite