Pb2+ promotes lipid oxidation and alterations in membrane physical properties

Experimental evidence suggests that cellular damage mediated by oxidants co uld be involved in the pathology associated with lead (Pb) toxicity. We inv estigated the effect of Pb2+ on lipid oxidation in liposomes using differen t initiators. In the presence of Fe2+ Pb2+ (12.5-200 mu M) Stimulated lipid oxidation in phosphatidylcholine:phosphatidylserine-containing liposomes, measured as 2-thiobarbituric acid-reactive substances (TBARS) and conjugate d dienes. This stimulatory effect depended on the presence of membrane nega tive charges and on bilayer integrity. Pb2+ did not stimulate TEARS formati on in the presence of 25 mM 2,2'-azo-bis (2,4 dimethylvaleronitrile (AMVN) and 2,2' azobis (2-amidinopropane) (AAPH). Pb2+ significantly stimulated TE ARS production and NADH oxidation in the presence of photoactivated rose Be ngal. The use of specific inhibitors indicated that several reactive oxygen species were involved in the pro-oxidant action of Pb2+. Pb2+ (12.5-200 mu M) caused membrane lateral phase separation and this effect was positively correlated with its capacity to stimulate Fe2+ and rose Bengal-initiated T EARS 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+ c ould be cytotoxic by altering membrane-related processes. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.