Truong Don H, Mihajlovic Aleksandra, Gunness Patrina, Hindmarsh Wayne, O'Brien Peter J
Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada.
Toxicology. 2007 Dec 5;242(1-3):16-22. doi: 10.1016/j.tox.2007.09.009. Epub 2007 Sep 15.
Recently, H(2)S (an environmental toxin) was proposed to induce cytotoxicity not only by inhibiting cytochrome oxidase but also by generating reactive oxygen species [Truong, D., Eghbal, M., Hindmarsh, W., Roth, Sh., O'Brien, P., 2006. Molecular mechanisms of hydrogen sulfide toxicity. Drug Metab. Rev. 38, 733-744]. In the following, evidence is presented supporting the use of hydroxocobalamin (vitamin B(12a)) as an antidote against H(2)S poisoning. More than 60% of the mice administered 35 mg/kg (0.63 mmol/kg) of NaSH (LD(90)) survived (at 24 h) when hydroxocobalamin (0.25 mmol/kg) was given after NaSH administration whereas less than 15% of the mice survived without hydroxocobalamin. Hydroxocobalamin (50-100 microM) or cobalt (50-100 microM) also prevented hepatocyte cytotoxicity induced by NaSH (500 microM). Furthermore, adding hydroxocobalamin 60 min later than NaSH still showed some protective activity. Catalytic amounts of hydroxocobalamin or cobalt added to a solution containing NaSH caused the disappearance of NaSH and induced oxygen uptake, indicative of NaSH oxidation and Co reduction, respectively.
最近，有人提出硫化氢（一种环境毒素）不仅通过抑制细胞色素氧化酶，还通过产生活性氧来诱导细胞毒性[特鲁昂，D.，埃格巴尔，M.，欣德马什，W.，罗斯，Sh.，奥布赖恩，P.，2006年。硫化氢毒性的分子机制。《药物代谢评论》38卷，733 - 744页]。以下提供的证据支持使用羟钴胺素（维生素B12a）作为硫化氢中毒的解毒剂。当在给予硫氢化钠（NaSH）后给予羟钴胺素（0.25毫摩尔/千克）时，超过60%给予35毫克/千克（0.63毫摩尔/千克）NaSH（LD90）的小鼠（在24小时时）存活，而没有羟钴胺素时存活的小鼠不到15%。羟钴胺素（50 - 100微摩尔）或钴（50 - 100微摩尔）也能预防由500微摩尔NaSH诱导的肝细胞细胞毒性。此外，在NaSH给药60分钟后添加羟钴胺素仍显示出一定的保护活性。向含有NaSH的溶液中添加催化量的羟钴胺素或钴分别导致NaSH消失并诱导氧摄取，这分别表明NaSH氧化和钴还原。
