Buzaleh Ana María, García-Bravo María, Navarro Susana, Morán-Jimenez María José, Méndez Manuel, Batlle Alcira, Fontanellas Antonio, de Salamanca Rafael Enríquez
Department of Biological Chemistry, Facultad de Ciencias Exactas y Naturales, Centro de Investigaciones Sobre Porfirinas y Porfirias (CIPYP), University of Buenos Aires, CONICET, Buenos Aires, Argentina.
Int J Biochem Cell Biol. 2004 Feb;36(2):216-22. doi: 10.1016/s1357-2725(03)00214-0.
Hepatoerythropoietic porphyria (HEP) is the homozygous form of Porphyria Cutanea Tarda (PCT), characterized by an accumulation of porphyrins due to uroporphyrinogen decarboxylase deficiency. Fluorinated volatile anaesthetics are often used to produce general anaesthesia. Anaesthesia has certainly been implicated in the triggering of acute porphyria crisis. The effects of volatile anaesthetics in a B-lymphocyte cell line established from HEP patients (LBHEP) on heme metabolism have been investigated.LBHEP cells were exposed to sodium phosphate buffer containing dissolved Enflurane, Isoflurane or Sevoflurane (10mM) during 20min. Aminolevulinate synthase (ALA-S) activity, the regulatory enzyme of heme synthesis, was 300% induced by the anaesthetics. A 25-30% diminution of porphobilinogenase (PBG-ase) activity was found when Isoflurane or Sevoflurane were added to the cells, while no significant changes were detected after Enflurane treatment. Although some oxidative stress has been induced by the anaesthetics, reflected by the 35% diminution of glutathione (GSH), no alteration in heme oxygenase (HO) activity, the enzyme involved in heme breakdown and frequently induced as a response to stress stimuli, was observed. Studies using animals inoculated with LBHEP cells were also performed. Findings here described mimic biochemical alterations in the heme pathway, which are characteristic of another hepatic porphyria, similar to those previously reported when these anaesthetics were administered to animals, and they also advertise about the possible unsafe use of these drugs in the case of hepatic non-acute porphyrias.
肝红细胞生成性卟啉病（HEP）是迟发性皮肤卟啉病（PCT）的纯合形式，其特征是由于尿卟啉原脱羧酶缺乏导致卟啉积聚。氟化挥发性麻醉剂常用于产生全身麻醉。麻醉肯定与急性卟啉病危机的触发有关。研究了挥发性麻醉剂对从HEP患者建立的B淋巴细胞系（LBHEP）中血红素代谢的影响。将LBHEP细胞在20分钟内暴露于含有溶解的恩氟烷、异氟烷或七氟烷（10mM）的磷酸钠缓冲液中。血红素合成的调节酶氨基乙酰丙酸合酶（ALA-S）活性被麻醉剂诱导增加300%。当向细胞中添加异氟烷或七氟烷时，发现胆色素原酶（PBG-ase）活性降低25-30%，而恩氟烷处理后未检测到显著变化。尽管麻醉剂诱导了一些氧化应激，表现为谷胱甘肽（GSH）减少35%，但未观察到血红素加氧酶（HO）活性的改变，HO是参与血红素分解且常因应激刺激而诱导的酶。还进行了使用接种LBHEP细胞的动物的研究。这里描述的发现模拟了血红素途径中的生化改变，这是另一种肝卟啉病的特征，类似于之前给动物施用这些麻醉剂时所报道的情况，并且它们还表明在肝非急性卟啉病的情况下使用这些药物可能不安全。
