Gupta Nidhi, Pant S C, Vijayaraghavan R, Rao P V Lakshmana
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, 474002, Gwalior, India.
Toxicology. 2003 Jun 30;188(2-3):285-96. doi: 10.1016/s0300-483x(03)00112-4.
The cyclic peptide toxins microcystins and nodularins are the most common and abundant cyanotoxins present in diverse water systems. They have been the cause of human and animal health hazards and even death. Over 60 microcystin variants have been reported so far. We report here the results of our study on comparative toxicity evaluation of three most predominant microcystins, MC-LR, MC-RR and MC-YR in mice. The mice were administered one LD(50) dose of MC-LR, RR and YR (43, 235.4 and 110.6 micro g/kg body weight, respectively), and biochemical and histological variables were determined at 30 min post-treatment and mean time to death (MTD). Significant increase in liver body weight index was induced by all three variants. There was marginal increase in serum levels of hepatic enzymes viz. AST, ALT and gamma-GT at 30 min post-treatment but 3-4 fold increase was observed at MTD. In contrast, enhanced LDH leakage, DNA fragmentation and depletion of hepatic glutathione was observed at 30 min post treatment in all three variants. There was no change in levels of serum protein, albumin and albumin/globulin ratio. Liver histology showed time dependent severe pathological lesions like congestion, haemorrhage, portal mononuclear cell infiltration and obliteration of chromatin material. Lung lesions were predominantly in bronchi and parenchyma. Though qualitatively lesions were identical in all three microcystin variants, degree of liver and lung lesions varied quantitatively with the toxin. The breathing pattern and respiratory frequency of the mice after i.p. administration of the toxin showed uniform pattern for 90 min followed by abrupt change in the respiratory pattern and instantaneous death. Based on biochemical and histological studies, MC-LR was found to be the most potent toxin followed by MC-YR and MC-RR.
环肽毒素微囊藻毒素和节球藻毒素是存在于各种水体系统中最常见且含量丰富的蓝藻毒素。它们已成为危害人类和动物健康甚至导致死亡的原因。迄今为止，已报道了60多种微囊藻毒素变体。我们在此报告对三种最主要的微囊藻毒素MC-LR、MC-RR和MC-YR在小鼠中进行比较毒性评估的研究结果。给小鼠分别腹腔注射一个半数致死剂量（LD(50)）的MC-LR、RR和YR（分别为43、235.4和110.6微克/千克体重），并在处理后30分钟和平均死亡时间（MTD）测定生化和组织学变量。所有三种变体均导致肝脏体重指数显著增加。处理后30分钟时，血清肝酶即天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和γ-谷氨酰转移酶（γ-GT）水平略有升高，但在平均死亡时间时观察到升高了3至4倍。相比之下，在处理后30分钟时，所有三种变体均观察到乳酸脱氢酶（LDH）泄漏增加、DNA片段化以及肝脏谷胱甘肽消耗。血清蛋白、白蛋白水平和白蛋白/球蛋白比值没有变化。肝脏组织学显示出随时间变化的严重病理损伤，如充血、出血、门静脉单核细胞浸润和染色质物质消失。肺部损伤主要发生在支气管和实质。尽管从性质上讲，所有三种微囊藻毒素变体的损伤相同，但肝脏和肺部损伤的程度随毒素量在数量上有所不同。腹腔注射毒素后小鼠的呼吸模式和呼吸频率在90分钟内呈现统一模式，随后呼吸模式突然改变并立即死亡。基于生化和组织学研究，发现MC-LR是最具毒性的毒素，其次是MC-YR和MC-RR。
