Carlsen E, Hetland O, Lindboe C F
Scand J Clin Lab Invest. 1983 Sep;43(5):445-51.
Based on earlier studies in rats, phospholipase C (PLC) seemed to be a very promising prophylactic agent for certain types of thrombo-embolic disease. Recent studies in rabbits have, however, demonstrated that phospholipase C is more toxic than expected from the previous data. To gain more knowledge about its toxicity in larger animals we have studied its effect in sheep. Estimated LD50 for the enzyme in sheep was between 0.4 and 0.2 mg PLC/kg given as a 23 min infusion and below 0.2 mg/kg given as a bolus. Cellular necrosis was a common feature in several tissues of sheep dying from PLC. This explained the pulmonary oedema, decreased oxygen tension and renal failure with haematuria, proteinuria and glucosuria which occurred. PLC was probably filtered out in the glomeruli and totally reabsorbed in the tubuli until they were destroyed by PLC. An increase in different plasma enzymes suggested that PLC exerted a toxic effect on both muscle cells and hepatocytes. The blood glucose level remained about 20% lower in the PLC-treated animals than in the controls for more than 2 weeks. Pulmonary oedema and renal failure were the probable causes of death.
基于早期对大鼠的研究，磷脂酶C（PLC）似乎是治疗某些类型血栓栓塞性疾病的一种非常有前景的预防药物。然而，最近对兔子的研究表明，磷脂酶C的毒性比先前数据预期的更大。为了进一步了解其在大型动物中的毒性，我们研究了它对绵羊的影响。以23分钟输注方式给药时，该酶在绵羊体内的半数致死剂量（LD50）估计在0.4至0.2毫克PLC/千克之间，推注给药时则低于0.2毫克/千克。细胞坏死是死于PLC的绵羊多个组织中的常见特征。这解释了所出现的肺水肿、氧分压降低以及伴有血尿、蛋白尿和糖尿的肾衰竭。PLC可能在肾小球中被滤过，并在肾小管中被完全重吸收，直到肾小管被PLC破坏。多种血浆酶的增加表明PLC对肌肉细胞和肝细胞均产生了毒性作用。在超过两周的时间里，接受PLC治疗的动物的血糖水平比对照组低约20%。肺水肿和肾衰竭可能是死亡原因。
