title: Volatile anaesthetics induce biochemical alterations in the heme pathway in a B-lymphocyte cell line established from hepatoerythropoietic porphyria patients (LBHEP) and in mice inoculated with LBHEP cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Buzaleh
authors.forename: María
authors.initials: M
authors.lastname: García-Bravo
authors.forename: Susana
authors.initials: S
authors.lastname: Navarro
authors.forename: María José
authors.initials: MJ
authors.lastname: Morán-Jimenez
authors.forename: Manuel
authors.initials: M
authors.lastname: Méndez
authors.forename: Alcira
authors.initials: A
authors.lastname: Batlle
authors.forename: Antonio
authors.initials: A
authors.lastname: Fontanellas
authors.forename: Rafael Enríquez
authors.initials: RE
authors.lastname: de Salamanca
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000494:pharmacology; D000642:Ammonia-Lyases / Q000378:metabolism; D000777:Anesthetics / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects*; D004737:Enflurane / Q000494:pharmacology; D006418:Heme / Q000737:chemistry; D006801:Humans; D007530:Isoflurane / Q000378:metabolism / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism; D008738:Methyl Ethers / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D018384:Oxidative Stress; D011164:Porphyrias / Q000188:drug therapy / Q000473:pathology*; D000077149:Sevoflurane; D013997:Time Factors
chemical_list: D000777:Anesthetics; D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D006418:Heme; D004737:Enflurane; D007530:Isoflurane; D000624:5-Aminolevulinate Synthetase; D000642:Ammonia-Lyases; C100132:porphobilinogenase