Stegelmeier B L, Molyneux R J, Elbein A D, James L F
USDA Agricultural Research Service, Poisonous Plant Research Laboratory, Logan, UT, USA.
Vet Pathol. 1995 May;32(3):289-98. doi: 10.1177/030098589503200311.
To better characterize and compare the toxicity of and lesions produced by locoweed (Astragalus mollissimus) with those of swainsonine and a related glycoside inhibitor, castanospermine, 55 Sprague-Dawley rats were randomly divided into 11 groups of five animals each. The first eight groups were dosed via subcutaneous osmotic minipumps with swainsonine at 0, 0.1, 0.7, 3.0, 7.4, or 14.9 mg/kg/day or with castanospermine at 12.4 or 143.6 mg/kg/day for 28 days. The last three groups were fed alfalfa or locoweed pellets with swainsonine doses of 0, 0.9, or 7.2 mg/kg/day for 28 days. Swainsonine- and locoweed-treated rats gained less weight, ate less, and showed more signs of nervousness than did controls. Histologically, these animals developed vacuolar degeneration of the renal tubular epithelium, the thyroid follicular cells, and the macrophage-phagocytic cells of the lymph nodes, spleen, lung, liver, and thymus. Some rats also developed vacuolation of neurons, ependyma, adrenal cortex, exocrine pancreas, myocardial epicytes, interstitial cells, and gastric parietal cells. No differences in lesion severity or distribution were detected between animals dosed with swainsonine and those dosed with locoweed. Rats dosed with castanospermine were clinically normal; however, they developed mild vacuolation of the renal tubular epithelium, the thyroid follicular epithelium, hepatocytes, and skeletal myocytes. Special stains and lectin histochemical evaluation showed that swainsonine- and castanospermine-induced vacuoles contained mannose-rich oligosaccharides. Castanospermine-induced vacuoles also contained glycogen. These results suggest that 1) swainsonine causes lesions similar to those caused by locoweed and is probably the primary locoweed toxin; 2) castanospermine at high doses causes vacuolar changes in the kidney and thyroid gland; and 3) castanospermine intoxication results in degenerative vacuolation of hepatocytes and skeletal myocytes, similar to genetic glycogenosis.
为了更好地描述和比较疯草（软毛黄芪）与苦马豆素及一种相关糖苷抑制剂（castanospermine）的毒性和所产生的损伤，将55只斯普拉格 - 道利大鼠随机分为11组，每组5只动物。前八组通过皮下渗透微型泵给予苦马豆素，剂量分别为0、0.1、0.7、3.0、7.4或14.9毫克/千克/天，或给予castanospermine，剂量为12.4或143.6毫克/千克/天，持续28天。最后三组分别喂食含有苦马豆素剂量为0、0.9或7.2毫克/千克/天的苜蓿或疯草颗粒，持续28天。与对照组相比，用苦马豆素和疯草处理的大鼠体重增加较少, 进食较少, 且表现出更多的紧张迹象。组织学上，这些动物的肾小管上皮细胞、甲状腺滤泡细胞以及淋巴结、脾脏、肺、肝脏和胸腺的巨噬细胞 - 吞噬细胞出现空泡变性。一些大鼠的神经元、室管膜、肾上腺皮质、外分泌胰腺、心肌上皮细胞、间质细胞和胃壁细胞也出现空泡化。在用苦马豆素给药的动物和用疯草给药的动物之间，未检测到损伤严重程度或分布的差异。用castanospermine给药的大鼠临床正常；然而，它们的肾小管上皮细胞、甲状腺滤泡上皮细胞、肝细胞和骨骼肌细胞出现轻度空泡化。特殊染色和凝集素组织化学评估表明，苦马豆素和castanospermine诱导的空泡含有富含甘露糖的寡糖。Castanospermine诱导的空泡也含有糖原。这些结果表明：1）苦马豆素引起的损伤与疯草引起的损伤相似, 可能是疯草的主要毒素；2）高剂量的castanospermine会导致肾脏和甲状腺出现空泡变化；3）castanospermine中毒导致肝细胞和骨骼肌细胞出现退行性空泡化，类似于遗传性糖原贮积病。
