TY - JOUR
T1 - Liposomal methemoglobin as a potent antidote for hydrogen sulfide poisoning
AU - Suzuki, Yuto
AU - Taguchi, Kazuaki
AU - Kure, Tomoko
AU - Enoki, Yuki
AU - Otagiri, Masaki
AU - Sakai, Hiromi
AU - Matsumoto, Kazuaki
N1 - Funding Information:
This study was financially supported by the Takahashi Industrial and Economic Research Foundation .
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/9/1
Y1 - 2022/9/1
N2 - 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.
AB - 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.
KW - Antidote
KW - Detoxification
KW - Hydrogen sulfide poisoning
KW - Liposome
KW - Methemoglobin
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U2 - 10.1016/j.taap.2022.116159
DO - 10.1016/j.taap.2022.116159
M3 - Article
C2 - 35803436
AN - SCOPUS:85133657924
SN - 0041-008X
VL - 450
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
M1 - 116159
ER -