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

• Published in: Archives of biochemistry and biophysics Vol. 305; no. 2; p. 282
• Main Authors: Oteiza, P I, Bechara, E J
• Format: Journal Article
• Language: English
• Published: United States 01-09-1993
• Subjects: Aminolevulinic Acid - chemistry; Cardiolipins - chemistry; Fatty Acids - chemistry; In Vitro Techniques; Lipid Peroxides - metabolism; Liposomes; Permeability; Phosphatidylcholines - chemistry; Vitamin E - pharmacology
• ISSN: 0003-9861
• DOI: 10.1006/abbi.1993.1424

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.