Kiss Márton, Petrikovics Ilona, Thompson David E
a Department of Chemistry , Sam Houston State University , Huntsville , TX , USA.
Hemoglobin. 2018 Sep-Nov;42(5-6):315-319. doi: 10.1080/03630269.2018.1553182.
Dimethyl trisulfide (DMTS) is a natural organic trisulfide that has been patented as a promising antidotal candidate against cyanide (CN). The primary mode of action of DMTS is as a sulfur donor that enables the conversion of CN to thiocyanate. Recently, it was discovered that DMTS is capable of oxidizing hemoglobin (Hb) to methemoglobin (MetHb) in vitro. The goal of these experiments was to measure the extent of DMTS-induced MetHb formation in vivo. In these experiments, intramuscular (IM) injections of formulated DMTS were administered to mice. Following the IM injection, blood was drawn and analyzed for MetHb using a rapid spectrophotometric method. Methemoglobin levels peaked in a dose-dependent manner between 20 and 30 min., and then began dropping. The highest MetHb levels measured for the 50, 100, 200 and 250 mg/kg doses of DMTS were respectively 3.28, 6.12, 9.69, and 10.76% MetHb. These experiments provide the first experimental evidence that IM administered DMTS generates MetHb in vivo and provide additional evidence for the presence of a secondary therapeutic pathway for DMTS - CN scavenging by DMTS-generated MetHb.
二甲基三硫醚（DMTS）是一种天然有机三硫化物，已获得专利，是一种有前景的氰化物（CN）解毒候选物。DMTS的主要作用方式是作为硫供体，使CN转化为硫氰酸盐。最近发现，DMTS在体外能够将血红蛋白（Hb）氧化为高铁血红蛋白（MetHb）。这些实验的目的是测量DMTS在体内诱导形成MetHb的程度。在这些实验中，给小鼠肌肉注射（IM）配制好的DMTS。肌肉注射后，采集血液，并用快速分光光度法分析MetHb。高铁血红蛋白水平在20至30分钟之间以剂量依赖方式达到峰值，然后开始下降。DMTS剂量为50、100、200和250mg/kg时测得的最高高铁血红蛋白水平分别为3.28%、6.12%、9.69%和10.76%高铁血红蛋白。这些实验提供了首个实验证据，即肌肉注射DMTS可在体内生成高铁血红蛋白，并为DMTS存在第二种治疗途径提供了额外证据——DMTS生成的高铁血红蛋白清除CN。
