Abstract

A large heterogeneous group of lysosomotropic compounds with a common cationic amphiphilic structure induces in vitro and in vivo lysosomal lipid storage. The biochemical mechanism underlying the lipidosis is still the subject of investigation. The authors report the experimental effect of imipramine and dexamethasone on lysosomal system in cultured skin fibroblasts. Morphological and ultrastructural observations of cells treated with imipramine showed vacuoles with lipidic storage, enlarged lysosomes with electron translucent zones and normal appearance of all the other cytoplasmic organelles. The lysosomal enzyme activities were decreased on biochemical study. On the contrary, an increased enzyme activity was detected in the culture medium. Pretreatment with dexamethasone partially prevented the effect of imipramine. Our results suggest that tricyclic antidepressants may induce lysosomal lipidosis through a dysfunction in the recycling of mannose-6-phosphate receptors and in the trafficking of newly synthesized lysosomal enzymes. Moreover the data presented may provide a clue in understanding some of the side effects observed in patients chronically treated with antidepressant drugs.