How affect volatile anaesthetics heme metabolism in control and different models of Porphyria. An update

BUZALEH ANA MARIA; MORAN JIMENEZ, MARIA JOSE; FONTANELLAS ANTONIO; ENRIQUEZ DE SALAMANCA RAFAEL; BATLLE ALCIRA

Dusseldorf

Congreso; INTERNATIONAL CONGRESS ON PORPHYRINS AND PORPHYRIAS 2015; 2015

Porphyrias can be classified according to the organwhere clinical expression of the biochemical defect is maximum either hepaticor erythropoietic, or according to the main clinical symptom  either acute or cutaneous. Acute IntermittentPorphyria (AIP) is due to a reduced activity of Porphobilinogen deaminase. ErythropoieticProtoporphyria (EPP) is an inherited deficiency of ferrochelatase that produceprotoporphyrin accumulation causing liver damage; these patients sometimes needliver transplantation that could lead to the development of a neuropathy like  that observed in acute porphyrias. Hepatoerythropoieticporphyria (HEP) is the homozygous form of Porphyria Cutanea Tarda (PCT), characterizedby an accumulation of porphyrins due to uroporphyrinogen decarboxylasedeficiency.  Anaesthesia is one of thefactors triggering acute attacks of acute porphyrias. Enflurane, Isoflurane andSevoflurane are volatile anaesthetics used to produce general anaesthesia. Theaim of this work was to make a brief review about the effect of thesexenobiotics on heme metabolism in control and genetic models of different typesof Porphyrias. In all  cases asignificant induction of 5-aminolevulinic acid synthetase (ALA-S) activity wasobserved  mimicking biochemicalalterations of heme pathway commonly observed in AIP patients, as a consequenceof a diminished PBG-D and a reduction of heme regulatory pool. Generally, hemecatabolism was altered whereby Heme oxygenase was induced, indicating theinstauration of oxidative stress that was confirmed by identifying oxidativeand nitrosative stress markers. Strain and sex differences were observed. Allour findings support that volatile anaesthetics would be non secure drugs to beadministered to individuals with a syndrome of acute porphyria and they alsoadvertise about the possible unsafe use of these drugs in the case of hepaticnon-acute porphyrias.