Department of Public Health, Division of Environmental Health Science, School of Health Sciences and Practice, New York Medical College, 40 Sunshine Cottage Rd, Valhalla, New York, 10595, USA; Department of Pediatrics, New York Medical College, 40 Sunshine Cottage Rd, Valhalla, New York, 10595, USA; Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava, 84505, Slovakia.
Department of Public Health, Division of Environmental Health Science, School of Health Sciences and Practice, New York Medical College, 40 Sunshine Cottage Rd, Valhalla, New York, 10595, USA.
Toxicol Lett. 2019 Jun 15;308:50-55. doi: 10.1016/j.toxlet.2019.03.014. Epub 2019 Mar 30.
Tetramethylenedisulfotetramine (TMDT) is a synthetic neurotoxic rodenticide and potential chemical threat agent. Signs of TMDT poisoning include convulsions which can progress into status epilepticus and death. Although clinical reports clearly show that poisoning via food and drink is the main route of exposure, experimental studies have primarily utilized parenteral routes. Here we used two different modes of oral administration of TMDT and compared the toxic outcomes with two different parenteral routes. Adult male mice were given various doses of TMDT either perorally in peanut butter or cereal pellets, or injected intraperitoneally (i.p.) or subcutaneously (s.c.). All routes produced the complete TMDT syndrome including twitches, clonic and tonic-clonic seizures and death. However potencies varied with the following rank order: i.p. > s.c. > oral (cereal)>>oral (peanut butter). Our data clearly show that ingestion of TMDT with peanut butter markedly reduces the overall syndrome severity relative to oral exposure via cereals. No significant differences were observed by substituting peanut oil for water as a vehicle for i.p. administered TMDT. In conclusion, high vs low fat food can differentially affect TMDT onset of action, probably due to differences in availability from the gastrointestinal tract. These results should be considered when searching for effective treatments for TMDT poisoning.
四亚甲基二砜四胺（TMDT）是一种合成的神经毒性杀鼠剂，也是一种潜在的化学威胁剂。TMDT 中毒的迹象包括抽搐，抽搐可能进展为癫痫持续状态和死亡。尽管临床报告清楚地表明，通过食物和饮料中毒是主要的暴露途径，但实验研究主要利用了肠外途径。在这里，我们使用了两种不同的口服 TMDT 给药方式，并将其与两种不同的肠外途径的毒性结果进行了比较。成年雄性小鼠通过口服花生酱或麦片丸、腹腔内（i.p.）或皮下（s.c.）注射给予不同剂量的 TMDT。所有途径均产生了完整的 TMDT 综合征，包括抽搐、阵挛和强直阵挛性发作和死亡。然而，效力随以下顺序变化：i.p.>s.c.>口服（麦片）>>口服（花生酱）。我们的数据清楚地表明，与通过麦片摄入 TMDT 相比，食用含花生酱的 TMDT 明显降低了整体综合征的严重程度。用花生油代替水作为 i.p. 给予 TMDT 的载体，没有观察到显著差异。总之，高脂肪和低脂肪食物可能会对 TMDT 的作用机制产生不同的影响，这可能是由于胃肠道的可用性不同。在寻找 TMDT 中毒的有效治疗方法时，应该考虑这些结果。
