EFFECT OF VANADATE ON 5-AMINOLEVULINIC SYNTHETASE IN A MURINE MODEL OF ACUTE INTERMITTENT PORPHYRIA.

JOHANNA ZUCCOLI; LEDA MARIA OLIVIERI; SILVINA FERNANDA RUSPINI; SANDRA MORAL; MARIA DEL CARMEN MARTINEZ; ALCIRA BATLLE; ANA MARIA BUZALEH; ESTHER NOEMI GEREZ

Burdeaux

Congreso; INTERNATIONAL CONGRESS ON PORPHYRINS AND PORPHYRIAS 2017; 2017

Acute Intermittent Porphyria (AIP) is characterized by an reduced activity of Porphobilinogen deaminase(PBG-D), increased levels of the first and rate limiting enzyme of heme pathway, 5-Aminolevulinicsynthetase (ALA-S) and the accumulation of neurotoxic precursors, ALA and porphobilinogen. ALA-S canbe induced by fasting or chemical agents. We have demonstrated that vanadate prevents thetranscriptional increase of ALA-S in a murine model of diabetes. The aim of this study was to investigatethe effect of vanadate on ALA-S in a murine model of AIP. Male and female knockout PBG-D deficientmice (Pbgd-/-) were divided in three experimental groups: non-fasted controls (C), fasted 24 hours (F)and vanadate (0.3 mg/ml in drinking water)+fasted (V+F). V was administered during 16 or 21 days. Asignificant lost of body weight was observed in males of F and V+F groups respect to C group, this effectwas not produced in females. Starvation increased the activity (100-500%, p