Liposomal methemoglobin as a potent antidote for hydrogen sulfide poisoning

Yuto Suzuki; Kazuaki Taguchi; Tomoko Kure; Yuki Enoki; Masaki Otagiri; Hiromi Sakai; Kazuaki Matsumoto

doi:10.1016/j.taap.2022.116159

Liposomal methemoglobin as a potent antidote for hydrogen sulfide poisoning

Toxicol Appl Pharmacol. 2022 Sep 1:450:116159. doi: 10.1016/j.taap.2022.116159. Epub 2022 Jul 5.

Authors

Yuto Suzuki¹, Kazuaki Taguchi², Tomoko Kure³, Yuki Enoki¹, Masaki Otagiri⁴, Hiromi Sakai³, Kazuaki Matsumoto¹

Affiliations

¹ Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
² Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. Electronic address: taguchi-kz@pha.keio.ac.jp.
³ Department of Chemistry, Nara Medical University, Shijo-cho 840, Kashihara, Nara 634-8521, Japan.
⁴ Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto City 860-0082, Japan; DDS Research Institute, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto City 860-0082, Japan.

PMID: 35803436
DOI: 10.1016/j.taap.2022.116159

Abstract

Hydrogen sulfide (H₂S) induces acute and lethal toxicity at high concentrations. However, no specific antidotes for H₂S poisoning have been approved. Liposomal methemoglobin (metHb@Lipo) was developed as an antidote for cyanide poisoning. As the toxic mechanism of H₂S poisoning is the same as that of cyanide poisoning, metHb@Lipo could potentially be used as an antidote for H₂S poisoning. In this study, we evaluated the antidotal efficacy of metHb@Lipo against H₂S poisoning. Stopped-flow rapid-scan spectrophotometry clearly showed that metHb@Lipo scavenged H₂S rapidly. Additionally, metHb@Lipo showed cytoprotective effects against H₂S exposure in H9c2 cells by maintaining mitochondrial function. MetHb@Lipo treatment also improved the survival rate after H₂S exposure in vivo, with the maintenance of cytochrome c oxidase activity and suppression of metabolic acidosis. Moreover, metHb@Lipo therapy maintained significant antidotal efficacy even after 1-year-storage at 4-37 °C. In conclusion, metHb@Lipo is a candidate antidote for H₂S poisoning.

Keywords: Antidote; Detoxification; Hydrogen sulfide poisoning; Liposome; Methemoglobin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antidotes / pharmacology
Antidotes / therapeutic use
Cyanides
Humans
Hydrogen Sulfide* / metabolism
Methemoglobin / metabolism
Methemoglobin / pharmacology
Poisoning* / drug therapy

Substances

Antidotes
Cyanides
Methemoglobin
Hydrogen Sulfide