Effects of porphyrinogenic agents on mitochondrial respiratory chain complexes

ZUCCOLI, JOHANNA; RUSPINI, SILVINA; BATLLE ALCIRA; BUZALEH ANA MARIA

Dusseldorf

Congreso; - INTERNATIONAL CONGRESS ON PORPHYRINS AND PORPHYRIAS 2015; 2015

Themitochondria play a vital role in energy metabolism, reactive oxygen speciesgeneration and cell death. Heme is one of the most biologically diversemolecules in nature; its deficiency by a reduced synthesis or an acceleratedcatabolism would trigger severe cell damage. Taking into account our previouswork demonstrating the multiplicity of brain metabolisms affected byporphyrinogenic agents, the aim was to elucidate if thereis any alteration on mitochondrial respiratory chain. The activities of I-III, II,II-III and IV complexes were measured in CF1male mice mitochondria encephalon treated with Isoflurane (2 ml/kg),Sevoflurane (1,5ml/kg), ethanol (30%), AIA (350 mg/kg), Veronal (167 mg/kg) andalso under food deprivation (24 hours). Results were compared in animals underpathological levels of 5-aminolevulinic acid (ALA, one or multiple doses, 40 mg/kg). Theactivity of I-III was induced by Isoflurane (169%, p<0.05) and in fasted mice(206%, p<0.05); although a decrease due to acute ALA (37%, p<0.05) was observed. ComplexII-III activity was induced by Sevoflurane (161%, p<0.05), while a diminutionwas produced by AIA (49%, p<0.05) and under fasting status (48%, p<0.05).When complex II was measured, an increased activity was detected after Sevoflurane(260%, p<0.05) and veronal (128%, (p<0.05) treatments while it wasdiminished by Isoflurane (36%, p<0.05), AIA (55%, p<0.05), and ethanol(54%, p<0.05). Complex IV activity augmented by fasting conditions (233%,p<0.05), Veronal treatment (207%, p<0.01) and acute ALA (162%, p<0.05), but it was decrease afterSevoflurane anaesthesia (34%, p<0.05). Results reinforce our previousreports and support the hypothesis that there would be more than one factor toexplain the pathogenesis of acute attacks. The damage to respiratory chainproduced by ALAwas observed only after acute administration and could be reflecting the pathophysiologicalcondition of porphyric patients.