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  • Title: Pb2+ promotes lipid oxidation and alterations in membrane physical properties.
    Author: Adonaylo VN, Oteiza PI.
    Journal: Toxicology; 1999 Jan 01; 132(1):19-32. PubMed ID: 10199578.
    Abstract:
    Experimental evidence suggests that cellular damage mediated by oxidants could be involved in the pathology associated with lead (Pb) toxicity. We investigated the effect of Pb2+ on lipid oxidation in liposomes using different initiators. In the presence of Fe2+, Pb2+ (12.5-200 microM) stimulated lipid oxidation in phosphatidylcholine:phosphatidylserine-containing liposomes, measured as 2-thiobarbituric acid-reactive substances (TBARS) and conjugated dienes. This stimulatory effect depended on the presence of membrane negative charges and on bilayer integrity. Pb2+ did not stimulate TBARS formation in the presence of 25 mM 2,2'-azo-bis (2,4 dimethylvaleronitrile (AMVN) and 2,2' azobis (2-amidinopropane) (AAPH). Pb2+ significantly stimulated TBARS production and NADH oxidation in the presence of photoactivated rose Bengal. The use of specific inhibitors indicated that several reactive oxygen species were involved in the pro-oxidant action of Pb2+. Pb2+ (12.5-200 microM) caused membrane lateral phase separation and this effect was positively correlated with its capacity to stimulate Fe2+ and rose Bengal-initiated TBARS production. Pb2+ could bind to the membrane and act to stimulate lipid oxidation by causing changes in membrane physical properties. Through this mechanism Pb2+ would favor the propagation of lipid oxidation. By causing lateral phase separation and/or by increasing lipid oxidation rates, Pb2+ could be cytotoxic by altering membrane-related processes.
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