Oxidative stress in brain of mice treated with different porphyrinogenic agents

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

Newport, Rhode Island, Estados Unidos

Congreso; GORDON RESEARCH CONFERENCE ON THE CHEMISTRY AND BIOLOGY OF TETRAPYRROLES; 2004

Gordon Research Conferences

Several drugs and stress are involved in the triggering of attacks in acute porphyrias. The central nervous system (CNS) is extremely sensitive to free radical damage because of a relatively low antioxidant capacity. We have previously demonstrated that brain cholinergic system in mice was altered by the administration of some porphyrinogenic agents and 5-aminolevulinic acid. 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. No alterations were observed in GSH levels. After acute anaesthesia with Enflurane or Isoflurane, MDA levels were 40% (p<0.01) diminished. Griseofulvin and Enflurane reduced 30% Gluthatione peroxidase activity. Superoxide dismutase activity was 57% diminished after acute anaestetic administration. Catalase activity diminished after AIA (35%, p<0.05) and dietary Griseofulvin (20%, p<0.05) administration. The activity of GSH reductase diminished after the administration of AIA (28%, p<0.05) and chronic anaesthesia witn enflurane (34%, p<0.01) or Isoflurane (37%, p<0.01). Porphyrinogenic agents caused a diminution or an increase in nitric oxide levels depending on the porphyrinogenic agent studied; these results would indicate a probably alteration on oxide nitric synthetase. 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 stress status was confirmed through HO induction