Munday R, Smith B L, Fowke E A
Ruakura Animal Research Centre, Ministry of Agriculture and Fisheries, Hamilton, New Zealand.
J Appl Toxicol. 1991 Apr;11(2):85-90. doi: 10.1002/jat.2550110203.
The short-term toxicity of 2-hydroxy-1,4-naphthoquinone (lawsone) and 2-methyl-1,4-naphthoquinone (menadione) has been compared in rats. 2-Methyl-1,4-naphthoquinone has been shown previously to cause haemolytic anaemia in animals, and this was confirmed in the present experiment. 2-Hydroxyl-1,4-naphthoquinone was found also to cause haemolysis, in a dose-dependent manner, as reflected by decreased blood packed cell volumes and haemoglobin levels and by histopathological changes in spleen, liver and kidney. With both naphthoquinones, the haemolysis was of the oxidative type, characterized by the presence of Heinz bodies within erythrocytes. Haemolysis was the only toxic change identified in rats dosed with 2-methyl-1,4-naphthoquinone. In contrast, 2-hydroxyl-1,4-naphthoquinone was not only a haemolytic agent but also a nephrotoxin, causing renal enlargement, elevated plasma levels of urea and creatinine and histologically-identified tubular necrosis, largely confined to the distal segment of the proximal convoluted tubules. The relationship between the in vivo toxic effects of these naphthoquinones and previously-reported data on their in vitro cytotoxic action is discussed.
已在大鼠中比较了2-羟基-1,4-萘醌(指甲花醌)和2-甲基-1,4-萘醌(维生素K3)的短期毒性。先前已证明2-甲基-1,4-萘醌可导致动物出现溶血性贫血,本实验证实了这一点。还发现2-羟基-1,4-萘醌也会以剂量依赖的方式引起溶血,这可通过血液红细胞压积和血红蛋白水平降低以及脾脏、肝脏和肾脏的组织病理学变化反映出来。对于这两种萘醌,溶血均为氧化型,其特征是红细胞内存在海因茨小体。溶血是给予2-甲基-1,4-萘醌的大鼠中唯一确定的毒性变化。相比之下,2-羟基-1,4-萘醌不仅是一种溶血剂,还是一种肾毒素,可导致肾脏肿大、血浆尿素和肌酐水平升高以及组织学鉴定的肾小管坏死,主要局限于近端曲管的远端段。讨论了这些萘醌的体内毒性作用与先前报道的它们的体外细胞毒性作用数据之间的关系。