A Sulfonyl Azide-Based Sulfide Scavenger Rescues Mice from Lethal Hydrogen Sulfide Intoxication

Yusuke Miyazaki, Eizo Marutani, Takamitsu Ikeda, Xiang Ni, Kenjiro Hanaoka, Ming Xian, Fumito Ichinose

Research output: Contribution to journalArticlepeer-review

Abstract

Exposure to hydrogen sulfide (H2S) can cause neurotoxicity and cardiopulmonary arrest. Resuscitating victims of sulfide intoxication is extremely difficult, and survivors often exhibit persistent neurological deficits. However, no specific antidote is available for sulfide intoxication. The objective of this study was to examine whether administration of a sulfonyl azide-based sulfide-specific scavenger, SS20, would rescue mice in models of H2S intoxication: Ongoing exposure and post-cardiopulmonary arrest. In the ongoing exposure model, SS20 (1250 μmol/kg) or vehicle was administered to awake CD-1 mice intraperitoneally at 10 min after breathing 790 ppm of H2S followed by another 30 min of H2S inhalation. Effects of SS20 on survival were assessed. In the post-cardiopulmonary arrest model, cardiopulmonary arrest was induced by an intraperitoneal administration of sodium sulfide nonahydrate (125 mg/kg) in anesthetized mice. After 1 min of cardiopulmonary arrest, mice were resuscitated with intravenous administration of SS20 (250 μmol/kg) or vehicle. Effects of SS20 on survival, neurological outcomes, and plasma H2S levels were evaluated. Administration of SS20 during ongoing H2S inhalation improved 24-h survival (6/6 [100%] in SS20 vs 1/6 [17%] in vehicle; p =. 0043). Post-arrest administration of SS20 improved 7-day survival (4/10 [40%] in SS20 vs 0/10 [0%] in vehicle; p =. 0038) and neurological outcomes after resuscitation. SS20 decreased plasma H2S levels to pre-arrest baseline immediately after reperfusion and shortened the time to return of spontaneous circulation and respiration. These results suggest that SS20 is an effective antidote against lethal H2S intoxication, even when administered after cardiopulmonary arrest.

Original languageEnglish
Pages (from-to)393-403
Number of pages11
JournalToxicological Sciences
Volume183
Issue number2
DOIs
Publication statusPublished - 2021 Oct 1

Keywords

  • antidotes
  • cardiopulmonary resuscitation
  • heart arrest
  • hydrogen sulfide
  • mice

ASJC Scopus subject areas

  • Toxicology

Fingerprint

Dive into the research topics of 'A Sulfonyl Azide-Based Sulfide Scavenger Rescues Mice from Lethal Hydrogen Sulfide Intoxication'. Together they form a unique fingerprint.

Cite this