In Vivo Interactions Between Cobalt or Ferric Compounds and the Pools of Sulphide in the Blood During and After H2S Poisoning
In Vivo Interactions Between Cobalt or Ferric Compounds and the Pools of Sulphide in the Blood During and After H2S Poisoning
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DOI：
10.1093/toxsci/kfu140
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发表时间：
2014-10-01
影响因子：
3.8
通讯作者：
Klingerman, Candice M.
中科院分区：
文献类型：
--
作者：
Haouzi, Philippe;Sonobe, Takashi;Klingerman, Candice M.
硫化氢是石油和天然气生产中的一种化学危害，最近已成为一种可怕的自杀方法，给急救人员带来了特定的风险和挑战。目前，还没有被证明有效的治疗方法来治疗硫化氢中毒及其严重的神经系统、呼吸系统或心脏后遗症。我们最近描述了，在硫化物暴露期间，硫化氢存在于体内的各种隔室或池中，具有不同程度的毒性。我们研究的总体目标是(1)确定在小型和大型哺乳动物暴露于硫化氢期间和之后，血液中各种硫化氢池的浓度和动力学，即气态(CGH(2)S)与总硫化物(即与一溴莫比胺反应)的浓度和动力学；(2)建立硫化氢池与高铁血红蛋白(MetHb)溶液或高剂量羟钴胺(HHCO)之间的相互作用。我们发现在镇静绵羊和大鼠输注硫化氢的过程中和输完硫化氢后，CGH(2)S在任何给定的输注速度/公斤下都是相似的，并在相同的CGH(2)下引起呼吸暂停和呼吸暂停等症状。停用硫化氢后，CGH(2)S在1分钟内消失。CMBBH_2S也下降到2-3亩M，但在至少30分钟内保持在高于基线水平。在输注H_2S的同时输注MetHb溶液仅使H_2S的游离池/可溶池立即减少，而CMBBH_2S增加了几倍。HYCO(70 mg/kg)还将游离/可溶性H_2S浓度降至几乎为零；CGH(2)如果维持H_2S输注，S最多在20分钟内恢复到H H_2O_2前水平。这些结果是在一个相关情景的背景下讨论的，其中解毒剂只能在接触硫化氢后才能使用。
Hydrogen sulphide (H2S), a chemical hazard in oil and gas production, has recently become a dreadful method of suicide, posing specific risks and challenges for the first responders. Currently, there is no proven effective treatment against H2S poisoning and its severe neurological, respiratory or cardiac after-effects. We have recently described that H2S is present in various compartments, or pools, in the body during sulphide exposure, which have different levels of toxicity. The general goals of our study were to (1) determine the concentrations and kinetics of the various pools of hydrogen sulphide in the blood, i.e., gaseous (CgH(2)S) versus total sulphide, i.e., reacting with monobromobimane (CMBBH2S), during and following H2S exposure in a small and large mammal and (2) establish the interaction between the pools of H2S and a methemoglobin (MetHb) solution or a high dose of hydroxocobalamin (HyCo). We found that CgH(2)S during and following H2S infusion was similar in sedated sheep and rats at any given rate of infusion/kg and provoked symptoms, i.e., hyperpnea and apnea, at the same CgH(2)S. After H2S administration was stopped, CgH(2)S disappeared within 1 min. CMBBH2S also dropped to 2-3 mu M, but remained above baseline levels for at least 30 min. Infusion of a MetHb solution during H2S infusion produced an immediate reduction in the free/soluble pool of H2S only, whereas CMBBH2S increased by severalfold. HyCo (70 mg/kg) also decreased the concentrations of free/soluble H2S to almost zero; CgH(2)S returned to pre-HyCo levels within a maximum of 20 min, if H2S infusion is maintained. These results are discussed in the context of a relevant scenario, wherein antidotes can only be administered after H2S exposure.