Jorge Rodriguez, Alcira Batlle & Ana Maria Buzaleh

Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP) - CONICET. University of Buenos Aires. Argentina

d-Aminolevulinic acid (ALA), a  heme precursor accumulated during the clinical expression of Acute Intermittent Porphyria (AIP), seems to be responsible for the neuropsychyatric manifestations of this syndrome. ALA-generated oxyradicals have been shown to cause oxidative lesions in rat brain synaptic membranes.

We have previously observed that Heme oxygenase activity in the brain of ALA treated animals, was induced  as an antioxidant response to protect this organ against the injury provoked by ALA. Moreover, ALA accumulation in whole brain was detected.

To determine if ALA provokes some alterations on the  brain antioxidant system, we have  investigated the effect of acute (a single dose of 40 mg/kg, ip.) and chronic (40 mg/kg every 48 hours during two weeks) ALA administration to mice on superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GRed) activities and TBARS and GSH levels.

A 56% (p<0.01) increase of TBARS levels was observed after acute ALA administration. Catalase activity was induced above 50% (p<0.05) after acute ALA treatment. Similar results were observed on GPx y GRed. No alterations were detected on SOD activity. In animals treated with chronic ALA, a minimal if any alteration was observed on the parameters assayed.

Data indicate that a rapid response to oxidative stress was developed against reactive oxidative species induced by ALA treatment. However, in long term intoxication,  the

redox balance was probably restored minimising oxidative damage.