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.