Yeong M L, Wakefield S J, Ford H C
Department of Pathology, Wellington School of Medicine, New Zealand.
Int J Exp Pathol. 1993 Apr;74(2):211-7.
Comfrey, a popular herbal remedy, contains hepatotoxic pyrrolizidine alkaloids and has been implicated in recent human toxicity. Although alkaloids from other plant sources have been extensively researched, studies on the hepatotoxic effects of comfrey alkaloids are scant. The effects of high dose comfrey toxicity have been studied and the present investigation was undertaken to identify changes associated with relatively low dose toxicity. Eight young adult rats were dosed weekly for six weeks with 50 mg/kg of comfrey derived alkaloids. The animals were dissected one week after the last dose and the livers examined by light and electron microscopy. Changes at the light microscopic level showed vascular congestion, mild zone 3 necrosis and loss of definition of hepatocyte cellular membranes. Extensive ultrastructural abnormalities were identified in the form of endothelial sloughing and the loss of hepatocyte microvilli. A striking finding was florid bleb formation on the sinusoidal borders of hepatocytes. Many blebs were shed into the space of Disse and extruded to fill, and sometimes occlude, sinusoidal lumina. Platelets were frequently found in areas of bleb formation. There was evidence of late damage in collagenization of Disse's space. Hepatocyte bleb formation is known to occur under a variety of pathological conditions but there is little to no information in the literature on the effects, if any, of bleb formation on fibrogenesis and the microcirculation and its role in the pathogenesis of liver disease. The pyrrolizidine alkaloids of comfrey may serve as an experimental tool to study the process of bleb formation and the intimate relationship between hepatocyte and sinusoidal injury in the liver.
紫草是一种常用的草药，含有肝毒性吡咯里西啶生物碱，近期已被证实与人体中毒有关。尽管来自其他植物来源的生物碱已得到广泛研究，但关于紫草生物碱肝毒性作用的研究却很少。高剂量紫草毒性作用已被研究，本研究旨在确定与相对低剂量毒性相关的变化。八只成年幼鼠每周给药一次，连续六周，剂量为50毫克/千克的紫草衍生生物碱。在最后一次给药一周后解剖动物，用光镜和电镜检查肝脏。光镜下的变化显示血管充血、轻度3区坏死以及肝细胞膜界限消失。通过内皮脱落和肝细胞微绒毛丧失的形式发现了广泛的超微结构异常。一个显著的发现是肝细胞窦状边界上出现大量小泡形成。许多小泡脱落到狄氏间隙并挤出以填充，有时会阻塞窦状腔。在小泡形成区域经常发现血小板。有证据表明狄氏间隙后期出现胶原化损伤。已知肝细胞小泡形成在多种病理条件下都会发生，但文献中几乎没有关于小泡形成对纤维化和微循环的影响（如果有的话）及其在肝病发病机制中的作用的信息。紫草中的吡咯里西啶生物碱可作为研究肝脏中小泡形成过程以及肝细胞与窦状损伤之间密切关系的实验工具。
