Department of Preventive Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan.
Department of Preventive Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan.
Toxicol Appl Pharmacol. 2021 Jan 1;410:115352. doi: 10.1016/j.taap.2020.115352. Epub 2020 Nov 29.
Epidemiological studies on chronic arsenic poisoning have clarified the relationship between various adverse effects and methylation efficiency or methylation capacity. However, no study has similarly investigated such effects on patients with acute arsenic poisoning. In the present work, we studied 61 patients with acute oral arsenic poisoning occurring after consumption of an arsenic trioxide-laced meal (curry soup). The cohort included children (defined as under 15 year old [y/o], n = 22) and adults (over 16 y/o, n = 39) whose urinary arsenic profiles were analyzed. None of these patients had received treatment with chelating agents. The estimated median (IQR) arsenic intake was 64.5 mg (48.3-80.5 mg) in children and 76.0 mg (56.0-91.0 mg) in adults, and these values were not significantly different. Symptoms of poisoning in children improved approximately 1 week after hospitalization. However, the symptoms in most adults deteriorated with severe signs of arsenic poisoning. Urinary arsenic profiles of all the patients were analyzed to obtain the following information: % monomethylarsonic acid (MMA), % dimethylarsinic acid (DMA), second methylation ratio (DMA/MMA), and secondary methylation index (SMI, DMA/MMA + DMA). The levels of these parameters may help identify patients at risk for worsening symptoms. %MMA, an indicator of incomplete methylation, increased more in adults, who experienced more severe symptom progression, compared with children. In contrast, %DMA, which indicates more complete and efficient methylation, increased particularly in children with mild symptoms. Overall the present results indicate that children possess an excellent capacity for methylation (second methylation ratio) of arsenic to DMA and therefore, experience relatively less severe progression of symptomology during acute arsenic poisoning.
流行病学研究阐明了慢性砷中毒与各种不良反应之间的关系,包括甲基化效率或甲基化能力。然而,目前尚无研究调查急性砷中毒患者的这些影响。本研究纳入了 61 例因食用含三氧化二砷的食物(咖喱汤)而发生急性口服砷中毒的患者。该队列包括儿童(定义为年龄小于 15 岁,n=22)和成人(年龄大于 16 岁,n=39),分析了他们的尿砷谱。这些患者均未接受螯合剂治疗。儿童的估计中位数(IQR)砷摄入量为 64.5mg(48.3-80.5mg),成人的为 76.0mg(56.0-91.0mg),差异无统计学意义。儿童住院后约 1 周内中毒症状改善,而大多数成人的症状恶化,出现严重砷中毒迹象。分析所有患者的尿砷谱以获得以下信息:单甲基砷酸(MMA)%、二甲基砷酸(DMA)%、二次甲基化率(DMA/MMA)和二次甲基化指数(SMI,DMA/MMA+DMA)。这些参数的水平可能有助于识别症状恶化风险较高的患者。未完全甲基化的指标 MMA 在经历更严重症状进展的成人中增加更多,而指示更完全和有效的甲基化的 DMA%则在症状较轻的儿童中增加更多。总的来说,本研究结果表明,儿童具有将砷甲基化为 DMA 的优异能力,因此在急性砷中毒期间,其症状进展相对较轻。