Morrow J D, Margolies G R, Rowland J, Roberts L J
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-6602.
N Engl J Med. 1991 Mar 14;324(11):716-20. doi: 10.1056/NEJM199103143241102.
The highest morbidity worldwide from fish poisoning results from the ingestion of spoiled scombroid fish, such as tuna and mackerel, and its cause is not clear. Histamine could be responsible, because spoiled scombroid fish contain large quantities of histamine. Whether histamine is the causative toxin, however, has remained in question. To address this issue, we investigated whether histamine homeostasis is altered in poisoned people.
The urinary excretion of histamine and its metabolite, N-methylhistamine, was measured in three persons who had scombroid-fish poisoning (scombrotoxism) after the ingestion of marlin. We measured 9 alpha, 11 beta-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid (PGD-M), the principal metabolite of prostaglandin D2, a mast-cell secretory product, to assess whether mast cells had been activated to release histamine.
The fish contained high levels of histamine (842 to 2503 mumol per 100 g of tissue). Symptoms of scombrotoxism--flushing and headache--began 10 to 30 minutes after the ingestion of fish. In urine samples collected one to four hours after fish ingestion, the levels of histamine and N-methylhistamine were 9 to 20 times and 15 to 20 times the normal mean, respectively. During the subsequent 24 hours, the levels fell to 4 to 15 times and 4 to 11 times the normal values. Levels of both were normal 14 days later. PGD-M excretion was not increased at any time. Two persons treated with diphenhydramine had prompt amelioration of symptoms.
Scombroid-fish poisoning is associated with urinary excretion of histamine in quantities far exceeding those required to produce toxicity. The histamine is most likely derived from the spoiled fish. These results identify histamine as the toxin responsible for scombroid-fish poisoning.
全球范围内，因食用变质的鲭科鱼类（如金枪鱼和鲭鱼）导致的鱼类中毒发病率最高，但其病因尚不清楚。组胺可能是病因，因为变质的鲭科鱼类含有大量组胺。然而，组胺是否为致病毒素仍存在疑问。为解决这一问题，我们研究了中毒者体内组胺稳态是否发生改变。
在三名食用枪鱼后发生鲭科鱼类中毒（鲭鱼中毒）的患者中，测量了组胺及其代谢产物N - 甲基组胺的尿排泄量。我们测量了前列腺素D2（一种肥大细胞分泌产物）的主要代谢产物9α，11β - 二羟基 - 15 - 氧代 - 2,3,18,19 - 四去甲前列腺素 - 5 - 烯 - 1,20 - 二酸（PGD - M），以评估肥大细胞是否被激活释放组胺。
这些鱼组胺含量很高（每100克组织含842至2503微摩尔）。食用鱼后10至30分钟出现鲭鱼中毒症状——脸红和头痛。在食用鱼后1至4小时采集的尿液样本中，组胺和N - 甲基组胺水平分别是正常均值的9至20倍和15至20倍。在随后的24小时内，水平降至正常值的4至15倍和4至11倍。14天后两者水平均恢复正常。PGD - M排泄量在任何时候都没有增加。两名接受苯海拉明治疗的患者症状迅速缓解。
鲭科鱼类中毒与组胺尿排泄量大幅增加有关，其增加量远超产生毒性所需水平。组胺很可能来源于变质的鱼。这些结果确定组胺是鲭科鱼类中毒的致病毒素。
