Heme oxygenase and stress markers in brain of mice treated with different porphyrinogenic agents

BATLLE, ALCIRA; RODRÍGUEZ, JORGE; LAVANDERA, JIMENA; MARTÍNEZ, MARIA DEL CARMEN; GEREZ, ESTHER; BUZALEH, ANA MARIA

Washington DC, EEUU

Congreso; EXPERIMENTAL BIOLOGY 2004; 2004

American Society for Pharmacology and Experimental Therapeutics

Heme oxygenase (HO), the rate-limiting step in heme degradation, is a heat-shock protein frequently induced by stress. Brain HO activity is largely attributed to HO-2. This organ has low activity of antioxidant enzymes. Several drugs and stress are involved in the triggering of attacks in acute porphyries. We have previously demonstrated that brain cholinergic system in mice was altered by the effect of some porphyrinogenic agents and 5-aminolevulinic acid administration. HO activity was induced after ALA challenge. The aim of this work was to evaluate the stress oxidative status in mice brain after the administration of known porphyrinogenic drugs. HO activity was induced by effect of Enflurane and Isoflurane, dietary griseofulvin and starvation. Anaesthetics also provoked an increased in mRNA HO expression. No alterations were observed in GSH levels. Griseofulvin and Enflurane reduced 30% Gluthatione peroxidase activity. Superoxide dismutase activity was 57% diminished after acute anaestetic administration. Catalase and Glutathione reductase activities, TBARS and nitric oxide levels were also measured. Data indicate that some of the drugs studied caused oxidative stress in brain and it could be one of the factors of porphyric neuropathy. The triggering of the antioxidant mechanism was confirmed through HO induction. This work was supported by grants of the Agencia de Promoción Científica y Tecnológica and the University of Buenos Aires