Ultrastructural and biochemical study of the action of benzoctamine and maprotiline on the rat liver

Stäubli, W.; Schweizer, W; Suter, J.; Hess, R.

doi:10.1007/bf01964942

Cited by 9 publications

(1 citation statement)

References 99 publications

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“…The presence of lysosomal enzymes within DIM bodies in cells of different organs and species, after the administration of various AP drugs, has been repeatedly demonstrated (25,32,41,(99)(100)(101)(102). Quantitative studies usually reveal increased activities of acid phosphatase, ,-glucuronidase, 3-galactosidase, and decreased activities of acid esterase, ,-N-acetylglucosaminidase and cathepsin D (62,72,88,(103)(104)(105)(106)(107)(108).…”

Section: Biochemical Studiesmentioning

confidence: 98%

Pulmonary and generalized lysosomal storage induced by amphiphilic drugs.

Hruban¹

1984

Environ Health Perspect

105

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Administration of amphiphilic drugs to experimental animals causes formation of myelinoid bodies in many cell types, accumulation of foamy macrophages in pulmonary alveoli and pulmonary alveolar proteinosis. These changes are the result of an interaction between the drugs and phospholipids which leads to an alteration in physicochemical properties of the phospholipids. Impairment of the digestion of altered pulmonary secretions in phagosomes of macrophages results in accumulation of foam cells in pulmonary alveoli. Impairment of the metabolism of altered phospholipids removed by autophagy induces an accumulation of myelinoid bodies. The administration of amphiphilic compounds thus causes pulmonary intra-alveolar histiocytosis which is a part of a drug-induced lysosomal storage or generalized lipidosis. The accumulation of drug-lipid complexes in myelinoid bodies and in pulmonary foam cells may lead to alteration of cellular functioning and to clinical disease. Currently over 50 amphiphilic drugs are known. Unique pharmacological properties necessitate clinical use of some of these drugs. The occurrence and severity of potential clinical side effects depend on the nature of each drug, dosage and duration of treatment, simultaneous administration of other drugs and foods, individual metabolic pattern of the patient and other factors. Further studies on factors preventing and potentiating adverse effects of amphiphilic drugs are indicated.ImagesFIGURE 1.FIGURE 2.FIGURE 3.FIGURE 4.FIGURE 5.FIGURE 6.FIGURE 7.FIGURE 8.FIGURE 9.FIGURE 10.

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