Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Toxicol Appl Pharmacol. 2022 Sep 1;450:116159. doi: 10.1016/j.taap.2022.116159. Epub 2022 Jul 5.
Hydrogen sulfide (HS) induces acute and lethal toxicity at high concentrations. However, no specific antidotes for HS poisoning have been approved. Liposomal methemoglobin (metHb@Lipo) was developed as an antidote for cyanide poisoning. As the toxic mechanism of HS poisoning is the same as that of cyanide poisoning, metHb@Lipo could potentially be used as an antidote for HS poisoning. In this study, we evaluated the antidotal efficacy of metHb@Lipo against HS poisoning. Stopped-flow rapid-scan spectrophotometry clearly showed that metHb@Lipo scavenged HS rapidly. Additionally, metHb@Lipo showed cytoprotective effects against HS exposure in H9c2 cells by maintaining mitochondrial function. MetHb@Lipo treatment also improved the survival rate after HS 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 HS poisoning.
硫化氢（HS）在高浓度下会引起急性和致命的毒性。然而，目前还没有专门针对 HS 中毒的解毒剂获得批准。载血红素（metHb@Lipo）被开发为氰化物中毒的解毒剂。由于 HS 中毒的毒性机制与氰化物中毒相同，因此 metHb@Lipo 可能可被用作 HS 中毒的解毒剂。在这项研究中，我们评估了 metHb@Lipo 对 HS 中毒的解毒效果。停流快速扫描分光光度法清楚地表明，metHb@Lipo 可以迅速清除 HS。此外，metHb@Lipo 通过维持线粒体功能，在 H9c2 细胞中显示出对 HS 暴露的细胞保护作用。metHb@Lipo 治疗还提高了 HS 暴露后体内的存活率，维持细胞色素 c 氧化酶的活性，并抑制代谢性酸中毒。此外，即使在 4-37°C 下储存 1 年后，metHb@Lipo 治疗仍保持显著的解毒效果。总之，metHb@Lipo 是 HS 中毒的一种候选解毒剂。
