OXIDATIVE TISSUE-RESPONSE PROMOTED BY 5-AMINOLEVULINIC ACID PROMPTLY INDUCES THE INCREASE OF PLASMA ANTIOXIDANT CAPACITY

The heme precursor 5-aminolevulinic acid (ALA), acting as a prooxidant , has been proposed to underlie the clinical manifestations of various porphyric disorders. Accordingly, ALA-generated oxyradicals where sho wn to cause oxidative lesions in biomolecules and isolated cell organe lles and to release iron from ferritin. In rats, administered ALA trig gered oxidative stress in liver, brain and red muscles. We now study t he correlation between the plasma antioxidant capacity and tissue oxid ative damage, after acute (one and two doses) and prolonged (eight dos es) ALA treatment of rats (one dose of ALA = 40 mg/kg body weight). Th e in situ spontaneous chemiluminescence intensity increased 5-fold in brain, 50% in liver and 4-fold in soleus muscle upon two dose-treatmen t, indicating tissue response to oxidative injury by ALA. Chemilumines cence reached the highest intensity after one or two doses of AI,A and decreased after eight doses in all tissues. The plasma trapping capac ity, evaluated by the luminol/2-amidinopropane system, gave a parallel response: maximum values after two doses and decreased values after p rolonged treatment. After eight doses, the AI,A concentration was foun d to be 3-fold above the normal value in plasma, 48% higher in liver a nd 38%, higher in total brain. These data indicate that the plasma ant ioxidant system responds to ALA treatment and is correlated with tissu e chemiluminescence. In vitro studies showed that ALA does not interfe re with the antioxidant plasma capacity, neither promoting oxidation o f plasma elements nor binding to plasma proteins.