5-aminolevulinic acid induces lipid peroxidation in cardiolipin-rich liposomes.

5-Aminolevulinic acid (ALA), a heme precursor accumulated in lead poisoning and acute intermittent porphyria, is known to undergo metal-catalyzed aerobic oxidation to yield reactive oxygen species. In phosphatidylcholine:cardiolipin (80:20) liposomes ALA (0.1-3.0 mM) promoted lipid peroxidation as evaluated by the formation of conjugated dienes and 2-thiobarbituric-reactive substances (TBARS). TBARS formation was dependent on ALA concentration and incubation time. ALA-induced lipid peroxidation was associated with an increase in liposome permeability as measured by the release of encapsulated carboxyfluorescein. alpha-Tocopherol (0.1-0.5 mol %), an efficient oxyradical scavenger, inhibits lipid peroxidation and prevents carboxyfluorescein release, suggesting that the permeabilization of liposomes is mainly due to lipid peroxidation. Cardiolipin, a major component of mitochondrial inner membrane, was particularly susceptible to ALA-induced lipid peroxidation. These results may be relevant to the previously observed Ca(2+)-dependent permeabilization of the inner membrane of rat liver mitochondria promoted by external 0.1-1.0 mM ALA; this mechanism has been implicated in the pathophysiology of acute intermittent porphyria and lead poisoning.