Pb2+ promotes lipid oxidation and alterations in membrane physical properties

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.