Drug-Induced Liver Reactions: A Morphological Approach

Altmann, Heidi

doi:10.1007/978-3-642-67861-5_3

Cited by 20 publications

(5 citation statements)

References 290 publications

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“…Thereby proliferation of inert lysosomal residual bodies, the lipofuscin, follows in the liver (Altmann 1980). Lipofuscin may accumulate in a similar way in renal epithelial cells in the course of an analgesic nephropathy (Laberke 1980).…”

Section: Discussionmentioning

confidence: 98%

Drug-induced lysosomal disorders in laboratory animals: new substances acting on lysosomes

Schneider¹

1992

Arch Toxicol

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Several substances with lysosomotropic activity were investigated in toxicological studies. AR-L 115 BS (sulmazol, a cardiotonic agent) was tested on beagle dogs; HX-CH 44 BS (a beta-blocker) and SX-AB 1316 SE (an antithrombotic agent) were tested on rats, and AF-CX 1325 XX (an antiepileptic agent) was tested on both rats and beagle dogs. All organ systems were examined morphologically by light and/or electron microscopy. When an increase in the number of lysosomes occurred this was confirmed by the pigment scheme according to Krutsay (1971) as well as by the detection of acid phosphatase and compared with earlier histochemical results. At higher dosages, all substances caused very marked proliferation of lysosomes in the liver and/or kidneys. HX-CH 44 BS also caused such proliferation in striated muscles and in the lungs. A brown discolouration of the kidneys was found with sulmazol and AF-CX 1325 XX. This finding corresponded to the microscopically detectable occurrence of numerous lipofuscin granules. The reticulum cells in the lymph nodes of dogs were also affected by AF-CX 1325 XX. It is concluded that the proliferation of lysosomes in various organs after administration of the above-mentioned substances is due to an excess of substance. The increased substance in the body is then stored in the lysosomes. With HX-CH 44 BS, lysosomal autodigestion of mitochondria in the skeletal musculature and in the alveolar macrophages of the lungs was found. The selective lysosomal incorporation of mitochondria has not been described up to now and in our opinion, this constitutes a special feature. The results otherwise largely correspond to those already described in the literature. Systemic phospholipidosis such as occurs with some other substances was not detectable. The incorporation of the substance causes several types of lysosomal inclusion. Uptake of the substance in lysosomes either leads to overt autodigestion of organelles such as mitochondria (HX-CH 44 BS) or peroxisomes or to residual lysosomes of dense structure which histochemically resemble lipofuscin. SX-AB 1316 SE serves as an example of a substance which is stored directly by lysosomes in crystalline form. Above all, in the liver the substance is taken up not only by the sinusoidal stellate cells but also by hepatocytes.

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Section: Discussionmentioning

confidence: 98%

Drug-induced lysosomal disorders in laboratory animals: new substances acting on lysosomes

Schneider¹

1992

Arch Toxicol

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“…The thyroid hormones and the cholestasis enzymes remained persistently elevated, even though the patient was under treatment. Since the cholestatic effect of carbimazole is well known (12), the treatment was interrupted. To our surprise the serum enzyme levels increased instead of decreasing.…”

Section: Discussionmentioning

confidence: 99%

Liver changes in patients with hyperthyroidism

Sola

Pardo-Mindan

Zozaya

et al. 1991

Liver

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ABSTRACT— We studied liver changes in the hepatic biopsies of five patients with hyperthyroidism. A characteristic histopathologic picture consisting of mild to moderate intrahepatocytic cholestasis, lobular inflammatory infiltrate with some eosinophils, and Kupffer cell hyperplasia was found in all cases. We discuss the specificity, clinico‐pathological correlations and the possible pathophysiology of these lesions.

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“…Yet microvesicular and vacuolar steatosis is by no means pathognomonic of VPA hepatotoxicity; instead it is nonspecific. This is also true for nonspecific and frequent cytotoxic lesions like cholestasis and necrosis of hepatocytes (Altmann, 1980). Ductular proliferation is also seen in varying degree in other liver diseases, e.g., in extrahepatic cholestasis, hepatitis, or liver fibrosis, especially in childhood (Roschlau, 1978;Thaler, 1987).…”

Section: Pathologic Anatomymentioning

confidence: 99%

Fatal Liver Failure in 16 Children with Valproate Therapy

et al. 1988

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The data of 16 children who died while receiving valproate (VPA) therapy in West Germany were analyzed. Five were normally developed, 5 were receiving VPA-monotherapy, and only 2 patients were aged less than 3 years. The first clinical symptoms of impending hepatotoxicity usually included nausea, vomiting, and apathy; pathologic laboratory tests reflected liver failure. Liver histology revealed microvesicular steatosis, cell necrosis, and bile duct proliferation of varying degree. An abnormal metabolite, 4-ene-VPA, was detected in all examined patients (six of six) and persisted after drug withdrawal. The pathogenesis of fatal liver failure during VPA treatment remains unknown. World-wide, approximately 100 fatalities have been reported in relation to VPA treatment. More than 90% were aged less than 20 years, 95% developed their first symptoms within the first 6 months of treatment, and 16 were treated with VPA alone. Since it is difficult precisely to define a group at risk for fatalities with VPA, careful clinical and laboratory monitoring with a special focus on vomiting and apathy, liver enzymes, and coagulation tests seem mandatory during the first 6 months after introduction of VPA. Taking into account the considerable number of fatalities during VPA treatment, the indication for its use requires careful reevaluation.

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Drug-Induced Liver Reactions: A Morphological Approach

Cited by 20 publications

References 290 publications

Drug-induced lysosomal disorders in laboratory animals: new substances acting on lysosomes

Drug-induced lysosomal disorders in laboratory animals: new substances acting on lysosomes

Liver changes in patients with hyperthyroidism

Fatal Liver Failure in 16 Children with Valproate Therapy

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