Pleiotropic effects of 5-aminolevulinic acid in mice brain

Abstract

5-Aminolevulinic acid (ALA) seems to be responsible for the neuropsychyatric manifestations of Acute Intermittent Porphyria (AIP). The aim was to study the effect of ALA on different metabolisms in mice brain to enhance our knowledge about the action of this heme precursor on the central nervous system. Heme metabolism, cholinergic system, defense enzyme system and nitric oxide metabolism were evaluated in encephalon mice receiving a single (40 mg/kg) or multiple doses of ALA (40 mg/kg, 14 days). We have found ALA accumulation in encephalon. ALA also altered the brain cholinergic system. After one dose of ALA, a decrease in Superoxide dismutase activity and a reduction of glutathione levels were detected, while malondialdehyde levels and Catalase activity were increased. Heme oxygenase was also increased as an antioxidant response to protect this organ against the injury. All Nitric Oxide Synthase isoforms were induced by ALA, being these changes more significant in glial cells for the inducible isoform. In conclusion, ALA affected several metabolisms in encephalon. Data indicate that a rapid response to oxidative stress was developed; however, in long term intoxication, the redox balance was probably restored minimizing oxidative damage.