The effect of lidocaine on cholesterol influx, esterification, and accumulation in cultured cells.
Lidocaine, a local anesthetic, inhibited cholesterol esterification in various cultured cells derived from tissues of the mouse, rat, hamster, monkey, and man. Esterification of exogenous [1-14C]oleate, fatty acid synthesized in situ from [1-14C]acetate, and exogenous [7-3H]cholesterol was reduced 20-50% with 1.5 mM lidocaine in the culture medium. In Fu5AH rat hepatoma cells, incubated for 24 h with hyperlipemic serum lipoproteins and increasing levels of lidocaine up to 1.5 mM, unesterified (free) cholesterol mass of the cells increased about 25% whereas the cholesteryl ester mass fell about 40%. The net result was a reduction in total cellular sterol. When the cells were incubated with lidocaine and hyperlipemic serum lipoproteins labeled with [7-3H(N)]cholesterol of known specific activity, incorporation of exogenous free cholesterol into cellular free cholesterol was constant, whereas there was a dose-dependent reduction in the amount of exogenous cholesterol appearing in cholesteryl esters. Additionally, a comparison of specific activities of cellular free cholesterol and cholesteryl esters at intervals over a 24-h period suggests that lidocaine also inhibits lysosomal cholesterol ester hydrolase (EC 3.1.1.13) in the Fu5AH cell line.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007739:L Cells; D008012:Lidocaine / Q000494:pharmacology*; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009829:Oleic Acids / Q000378:metabolism; D051381:Rats; D002785:Sterol O-Acyltransferase / Q000378:metabolism
D000085:Acetates; D009829:Oleic Acids; D002784:Cholesterol; D008012:Lidocaine; D002785:Sterol O-Acyltransferase