Antioxid Redox Signal. 2013 Aug 10;19(5):510-6. doi: 10.1089/ars.2012.4513. Epub 2012 Mar 6.
To sort out the putative roles of endogenous hydrogen sulfide (H2S) in clinical conditions wherein systemic inflammation or hypoxia is present, it becomes crucial to develop approaches capable of affecting H2S concentration that can be safely applied in humans. We have investigated a paradigm, which could achieve such a goal, using vitamin B12 (vit.B12), at the dose recommended in cyanide poisoning, and very low levels of methemoglobin (MetHb). Hydroxocobalamin in the plasma, supernatant of kidney, and heart tissue homogenates of rats that had received vit.B12 (140 mg.kg(-1) intravenous) was found in the μM range. Exogenous H2S (100 μM) added to the plasma or supernatants of these rats decreased at a significantly higher rate than in control rats. In the latter however a spontaneous oxidation of exogenous H2S occurred. In vitro, hydroxocobalamin solution (100 μM) decreased, within <2 min, an equimolar concentration of H2S by 80%. Three to five percent MetHb prevented H2S induced hyperventilation in vivo and decreased exogenous H2S in vitro by 25-40 μM within 30 s. Our observations lead to the hypothesis that innocuous levels of MetHb and vit.B12 could be a used as an effective and safe way to test the role of endogenous H2S in vivo.
为了厘清内源性硫化氢(H2S)在存在全身炎症或缺氧的临床情况下的潜在作用,开发出能够影响 H2S 浓度的方法变得至关重要,而这些方法必须是安全应用于人体的。我们已经研究了一种使用维生素 B12(vit.B12)的范式,可以达到这样的目标,vit.B12 的剂量是氰化物中毒推荐的剂量,并且只有非常低水平的高铁血红蛋白(MetHb)。在接受 vit.B12(140 mg.kg(-1) 静脉注射)的大鼠的血浆、肾脏上清液和心脏组织匀浆中,羟钴胺的浓度在μM 范围内。向这些大鼠的血浆或上清液中添加 100 μM 的外源性 H2S 会以比对照组更快的速度减少。然而,在后一组中,外源性 H2S 会自发氧化。在体外,羟钴胺溶液(100 μM)在<2 分钟内将等摩尔浓度的 H2S 减少了 80%。3%至 5%的 MetHb 可防止体内 H2S 诱导的过度通气,并在 30 秒内使体外的外源性 H2S 减少 25-40 μM。我们的观察结果导致了这样一种假设,即无害水平的 MetHb 和 vit.B12 可以作为一种有效和安全的方法,用于在体内测试内源性 H2S 的作用。