Lysosomes and tegument pathology in the chemotherapy of schistosomiasis with 1,7 -<i>bis</i>(<i>p</i>-aminophenoxy)heptane(153C51)

Watts, Stuart D.M.; Orpin, A.; MacCormick, C.

doi:10.1017/s0031182000051155

Cited by 21 publications

(7 citation statements)

References 18 publications

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“…4E). Similar suggestions have been presented by Watts, Orpin & MacCormick (1979) who observed the dynamics of consequent activation and exhaustion of AP activity in the tegument of Schistosoma mansoni following treatment with \,l-bis/paminophenoxy/heptane.…”

Section: Discussionsupporting

confidence: 83%

“…The morphological and cytochemical data obtained herein as well as those of other authors (Watts et al 1979;Simpson & McLaren, 1982;Rogan & Richards, 1986;Stoitsova & Dacheva, 1987;Gorchilova et al 1991) may be summed up in the supposition that the tegument of cestodes and trematodes is able to activate its otherwise relatively inactive lysosomal system under the damaging action of a variety of agents.…”

Section: Discussionsupporting

confidence: 69%

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Effects of three anthelmintics on the tegument ofHymenolepis fraterna(Cestoda)

1992

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The in vivo effects of the anthelmintics taenifugin, VUFB 14170 and VUFB 15269 on the tegument of Hymenolepis fraterna have been examined by SEM, TEM and cytochemistry. The drugs were given to H. fraterna-infected mice on the 14th day post-infection in a single oral dose of 150, 200 and 200 mg/kg, respectively. By 72 h post-treatment, the drug-induced pathomorphological changes in the tegument indicated that all three drugs had a significant effect. Changes were most pronounced on the brush border and in the intercellular material. On the apical surface, there was blebbing as well as accumulation of membrane fragments over the microthrix tips and erosion of the brush border. The intercellular material was changed in structure, showing increased electron density in some areas and oedema of the intercellular spaces in other areas. There were also fractures of the tegument of variable depth, sometimes reaching to the parenchyma. These results suggest altered tegumental integrity and, occasionally, complete disruption of the selective permeability barrier created by the normal tegument. This suggestion is further supported by the penetration of ruthenium red into some tegumental areas and its distribution into the intercellular spaces, down to the parenchyma. The intrategumental lysosomes also appeared to be significantly activated. There was evidence of autophagy in both distal cytoplasm and tegumental cells. Mature and gravid proglottides were more susceptible to drug damage than those in the anterior strobila and neck.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 69%

Effects of three anthelmintics on the tegument ofHymenolepis fraterna(Cestoda)

1992

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“…Multivesicular bodies in the region of Golgi apparatus in the tegument of adult schistosomes that have similar appearance to lysosomes were described by . However, they suggested there was limited lysosomal activity in the system (Wilson & Barnes, 1974 b), though acid phosphatase activity was detected in the adult worm tegument using cytochemical procedures (Bogitsh & Krupa, 1971 ;Watts, Orpin & MacCormick, 1979). In this paper we present observations on the lysosome-like acidic compartments of schistosomula.…”

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confidence: 84%

The properties of acidic compartments in developing schistosomula ofSchistosoma mansoni

et al. 2003

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A variety of fluorescent probes have been used to study the acidic compartments in cercariae and schistosomula of Schistosoma mansoni. Freshly transformed schistosomula treated with the LysoTracker Red dye specific for lysosomes showed large acid-containing compartments (0.5-10 microm in size). The uptake of the dye is an energy-dependent process that depends on the metabolic activity of schistosomula. The compartments were quantified individually with respect to area, quantity of fluorescence and the total number/schistosomulum. Under normal conditions these compartments were not found in untreated cercariae, but appeared in cercariae slightly damaged by poly-L-lysine. The formation of these compartments seemed to be related to the development of cercariae into schistosomula as the number of compartments and uptake of fluorescence increased with time after transformation. Also, the method of transformation as well as the in vitro incubation of the parasite affected the percentage area of compartments/schistosomulum. Acid phosphatase enzyme activity was assessed using an endogenous phosphatase probe. Living and fixed schistosomula displayed the presence of enzyme activity in compartments of the same size and distribution as the acid-rich compartments. This was confirmed by histochemical staining showing deposition of enzyme-generated lead at the sites of phosphatase activity. We suggest that the development of acidic compartments is important during the transformation process or as a consequence of damage.

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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). The levels of several lysosomal enzymes (particularly that of ,B-N-acetylglucosaminidase) of foam cells are increased, while acid esterase and a-manosidase are decreased (23,88,109,110).…”

Section: Biochemical Studiesmentioning

confidence: 99%

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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Lysosomes and tegument pathology in the chemotherapy of schistosomiasis with 1,7 -bis(p-aminophenoxy)heptane(153C51)

Cited by 21 publications

References 18 publications

Effects of three anthelmintics on the tegument ofHymenolepis fraterna(Cestoda)

Effects of three anthelmintics on the tegument ofHymenolepis fraterna(Cestoda)

The properties of acidic compartments in developing schistosomula ofSchistosoma mansoni

Pulmonary and generalized lysosomal storage induced by amphiphilic drugs.

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