Lipidosis-like alterations in cultured macrophages exposed to local anaesthetics.

In this ultrastructural study, the simple model of cultured rat peritoneal macrophages was used to examine whether local anaesthetics can induce lipidosis-like alterations. Exposure (24h) of macrophages to 1 X 10(-5) M dibucaine, or to 5 X 10(-5) M tetracaine, quinidine, and quinine, respectively, led to the occurrence of lamellated cytoplasmic inclusions in most cells. This is interpreted as indicating lipidosis. Type and degree of alterations were similar to those induced by the reference compound chlorphentermine (5 X 10(-5) M) for which lipidosis has previously been shown by biochemical methods. Tocainide (5 X 10(-5) M) caused weak alterations only; procaine (5 X 10(-5) M) was without effect. The differential potencies presently observed are paralleled by differential affinities of the local anaesthetics towards polar lipids as determined by other authors. The present results support the hypothesis that the lipidosis-inducing potency inherent to an amphiphilic cationic drug can be tentatively predicted on the basis of its affinity to polar lipids, although it may be obscured by secondary factors when the drug is administered to intact organisms. The present communication emphasizes the advantage of cell cultures over animal experiments for studying the structure-response relationships underlying drug-induced lipidosis, and to reliably ascertain that a given drug has only low lipidosis-inducing potency or none at all as found for tocainide and procaine, respectively.