Oxidative stress in acute intermittent porphyria and lead poisoning may be triggered by 5-aminolevulinic acid
Braz. j. med. biol. res
; 29(7): 841-51, July 1996. ilus
Artigo
em Inglês
| LILACS
| ID: lil-181496
Biblioteca responsável:
BR1.1
RESUMO
Highly reactive oxyradicals can be generated in vitro by iron-catalyzed aerobic oxidation of synthetic and naturally occuring substances capable of enolization in aqueous medium. Of biological interest are alfa-hydroxy- and alfa-aminocarbonyls such as carbohydrates, 5-aminolevulinic acid, and aminoacetone which tautomerize to the corresponding enediols and enolamines and yield oxyradicals initiated by electron transfer to dioxygen. Free radicals have been implicated in several normal and pathological processes. We briefly review our hypothesis of an in vivo prooxidant role of 5-aminolev-ulinic acid (ALA), the heme precursor accumulated in several porphyric disorders (e.g., lead poisoning, acute intermittent porphyria (AIP), tyrosinosis). Accordingly, i) ALA undergoes transition metal-catalyzed oxidation to give O-2, H2O2 and HO; ii) ALA induces iron release from ferritin, lipid peroxidation of cardiolipin-rich vesicles, single strand breaks in plasmid DNA, and guanosine oxidation in calf thymus DNA; iii) ALA causes Ca2+ -mediated rat liver mitochondria permeabilization; iv) rats chronically treated with ALA exhibit increased glycolytic metabolism; v) brain extracts of ALA-treated rats reveal increased levels of thiobarbituric acid reactive substances, direct chemiluminescence intensity, carbonyl proteins, ferritin, and "free iron"and gama-aminobutyric acid-receptor dissociation constant, and vi) patients with AIP and lead-exposed workers present augmented erythrocytic levels of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. These data indicate the involvement of ALA-generated reactive species in the clinical manifestations (neuropathy, mental changes, muscle weakness, hepatoma) shared by the aforementioned inherited and acquired porphyric diseases.
Buscar no Google
Coleções:
Bases de dados internacionais
Base de dados:
LILACS
Assunto principal:
Espécies Reativas de Oxigênio
/
Porfiria Aguda Intermitente
/
Estresse Oxidativo
/
Ácido Aminolevulínico
/
Intoxicação por Chumbo
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Braz. j. med. biol. res
Assunto da revista:
Biologia
/
Medicina
Ano de publicação:
1996
Tipo de documento:
Artigo
/
Congresso e conferência
