Mitochondrial respiratory chain alterations due to porphyrinogenic agents in a mouse model of Acute Intermittent Porphyria

ZUCCOLI, JOHANNA; MARTINEZ MARIA DEL CARMEN; BATLLE, ALCIRA; RUSPINI, SILVINA; BUZALEH ANA MARIA

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2016

Sociedad Argentina de Investigación Clínica (SAIC)

The mitochondria play a vital role in energy metabolism, reactive oxygen species generation and cell death. Heme is one of the most biologically diverse molecules in nature; its deficiency by a reduced synthesis or an accelerated catabolism would trigger severe cell damage. Previously we demonstrated that porphyrinogenic agents affected several brain metabolisms included respiratory mitochondrial chain in encephalon CF1 mice. The aim was to study the effects of volatile anaesthetics and other xenobiotics on the activity of I to IV complexes of respiratory chain in a mouse model of Acute Intermittent Porphyria. For this purpose we use male knockout mice that have 50% reduced the activity of the enzyme Porphobilinogen deaminase, treated with Isoflurane (2 ml/kg), Sevoflurane (1,5ml/kg), ethanol (30%), allylisopropylacetamide (AIA, 350 mg/kg) and Veronal (167 mg/kg). The activities of I-III, II-III, II and IV complexes were measured in mitochondria of encephalon. Veronal increased the activity of II-III complexes (370%; p