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

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

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Sociedad Argentina de Investigación Clínica (SAIC)

The mitochondria play a vital role in energy metabolism; inside occursoxidative phosphorylation in the electron transport chain and thegeneration of reduction equivalents by the tricarboxylic acid (TCA)cycle. Heme deficiency produced by a reduced synthesis or an acceleratedcatabolism would trigger severe cell damage. Previouslywe demonstrated that porphyrinogenic agents affected several brainmetabolisms included respiratory mitochondrial chain in encephalonCF1 and Acute intermittent Porphyria (AIP) genetic modelmice.The aims were to study the effects of volatile anesthetics and otherxenobiotics on the activity of fumarase and aconitase in a mousemodel of AIP; and to analyze if there are protein and lipid damagedue to these treatments. For these purposes we use male knockoutmice that have 50% reduced the activity of Porphobilinogen deaminase.Animals were treated with Isoflurane (2 ml/kg), Sevoflurane(1,5ml/kg), ethanol (30%), allylisopropylacetamide (AIA, 350 mg/kg), Veronal (167 mg/kg) or starved (24 hs). The enzymes activitieswere measured in mitochondria of encephalon. Fumarase activitydecreased due to Isoflurane (30%; p