| Summary: | Our mini-review concerns the potential adverse pro-oxidant role of 5-aminolevulinic (ALA), the first protoporphyrin IX (PP-IX)/heme precursor widely used in commercial formulations for endogenous photodynamic therapy (PDT). Our account collates the two sides of (i) ALA aerobic oxidation as a source of H2O2 and radicals when accumulated in acute intermittent porphyria (AIP), hereditary tyrosinemia type 1 (HT1), and lead poisoning, thereby triggering similar biochemical damage and symptoms and (ii) the central role of PP-IX as the immediate precursor of the heme prosthetic group of key proteins and enzymes (hemoglobin, myoglobin, cytochromes, catalase, and others). Conversely, PP-IX induces skin photodamage when accumulated in sun-exposed erythropoietic protoporphyria (EPP) patients. Furthermore, we highlight the harnessing of such antithetical ALA and PP-IX properties to design efficient PDT and insecticidal strategies. Research on ALA-based PDT photosensitizers calls for more attention on the deleterious action of excess ALA, whose main target is the mitochondrion.
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