Fenfluramine-induced ultrastructural alterations in tissues of rats and guinea pigs

Summary

After administration of the anorectic drug fenfluramine (40 mg/kg per day) to rats (s. c. or i. p.) and guinea pigs (p.o.) over periods of 2 to 11 weeks, electron microscopic examination was performed on lungs, liver, lymphatic tissues and peripheral blood of both species, and on adrenal glands and ovaries of rats. In rats, fenfluramine caused the following alterations (listed according to the duration of treatment): Formation of abnormal lamellated inclusions in lymphocytes and plasma cells of lymphatic tissues, appearance of “foam cells” in lung alveoli; formation of abnormal lamellated inclusions in corpus luteum, lymphocytes of peripheral blood, and in adrenal cortex. In guinea pigs, the same alterations were found in lymphocytes of spleen and peripheral blood, in hepatocytes and in lung.

The present observations support the concept of a generalized phospholipidosis induced by amphiphilic compounds. The potency of fenfluramine to induce a lipidosis is, however, considerably less pronounced than that previously demonstrated for the anorectic drug chlorphentermine. This difference is suggested to be due mainly to the lower degree of amphiphilia of fenfluramine.