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.
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.
Buzaleh
Ana María
AM
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.
García-Bravo
María
M
Navarro
Susana
S
Morán-Jimenez
María José
MJ
Méndez
Manuel
M
Batlle
Alcira
A
Fontanellas
Antonio
A
de Salamanca
Rafael Enríquez
RE
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
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