AmBisome is a true single bilayer liposomal drug delivery system. Liposomes consists of these unilamellar bilayer liposomes with amphotericin B intercalated. Efectividad de anfotericina B liposomal en pacientes ingresados en UCI con técnicas de reemplazo renal. RESUMEN. Introducción. Comparar la efectividad de. La leishmaniasis cutánea es una zoonosis producida por diferentes especies del parásito del género Leishmania. Existen 2 tipos de leishmaniasis, la que se.

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The aim of our study was to compare the nephrotoxic effects of liposomal Amphotericin B Ambisome and Amphotericin B lipid complex Abelcet on rat kidneys at short 14 days and long term 28 days treatment applications. Groups 1 and 4 are composed as control groups by administrating intraperitoneal ip 0, 9 molar Serum physiologic for a period of 14 and 28 days respectively.

Then, the rats were transcardially perfused, samples were taken from cortex and medulla regions of kidneys. The micrographs of group 1 and 4 were seen as normal. For short term treatment, some morphological changes were seen in proximal tubule cells in group 3 whereas in group 2 the graphs were observed as normal.

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However, after long term drug using in group 5 and 6 there were vacuolization, increased lysosomal structures and deep basal folding’s into tubular g lumen. These experiments establish that renal damage were seen in short and long term use of Abelcet and long term use of Ambisome. H B lipid formulations; Rat kidney; Nephrotoxicity; Ultrastructure. Amphotericin B is a natural antibiotic belonging to the polyene group, isolated in from a strain of the actinomycete streptomyces nodosus and it is a key agent in the management of serious systemic fungal infections.

However, Amphotericin B has been introduced clinically, a number of acute and chronic toxicities have made the treatment with this anfoteridina difficult for patients to tolerate. Moreover, it has been reported that nephrotoxicity is the most common serious adverse effect of Amphotericin B Gallis et al. Even in the setting of maximally tolerated doses of Amphotericin B is frequently fails to control invasive fungal infections, especially in the immunocompromised host. These lipids based on to have less nephrotoxic effects than conventional Amphotericin B even at higher doses lipowomal they are in the early stages of clinical trials Doubek et al.

Liposomal Amphotericin B and Leishmaniasis: Dose and Response

Meanwhile, Sun et al. Prior studies were shown that there have been better tolerance lipoomal these formulations, but no effectual data exist regarding the comparison of ultrastructural effects of Amphotericin B lipid complex ABLC and liposomal Amphotericin B L-AMB in kidney. Therefore, the present study was undertaken to investigate morphologically the effects of administration of two separate Amphotericin B lipid formulations- Liposomal Amphotericin B L-AMB, Ambisome and Amphotericin lipid complex ABLC, Abelcet on rat kidney at short and long term application periods.

The animals were divided into 6 anfotfricina each including six rats: From each kidney, the tissue samples were taken from the cortex and medullar regions which were 1 mm3 thick. Ultrathin sections were obtained from selected areas, stained with uranyl acetate and lead citrate, and examined with a Zeiss EM transmission electron microscope.

Groups 1 and 4 Control groups: There were no apparent damages in glomerular structures and renal tubules. The spherical anfoericina elongated mitochondria were normal appearance in the tubular epithelial cells. Endoplasmic reticulum cisternae, small vacuoles and lysosomes were located between them. High, thin and parallel microvilli were observed on the apical surface of epithelial cells of tubules Fig.

Moreover, the ultrastructural examination revealed normal glomerular basement membrane and normal foot process organization Fig. Group 2 treated with Ambisome for 14 days: Tubular cells appeared nearly normal. The distribution, size and shape of mitochondria and endoplasmic reticulum were normal both in proximal and distal tubular cells Figs. Glomerular structures and basement membrane were seen normal as in control groups.


Group 3 treated with Abelcet for 14 days: Epithelial cells of proximal and distal tubules were nearly normal. Nucleus, mitochondria, endoplasmic reticulum were all normal in morphological appearance.

Liposkmal, on apical cytoplasm lots amount of lysosomes and different size of vacuolar structures were exhibited Fig. In some cells, vacuolar structure was increased and lytic areas were also seen in cytoplasm Fig. Tubular and glomerular basement membranes were normal. Group 5 treated with Ambisome for 28 days: Vacuolar structures and lysosomes were increased in proximal tubule epithelial cells.

Most of these cells, the basal laminae were seen in normal thicknesses; in some proximal tubule cells deep basal foldings were seen Fig. Some of the cells made protrusion into the lumen.

In these cells, increased lysosomes were also seen Fig. In distal tubule cells, same ultrastructural changes exhibited like proximal tubule cells. In these cells deep basal foldings were seen. Moreover, huge of vacuolar structures were also found. These different shaped vacuolar structures were rounded with membrane whether, in cytoplasm place to place they were incorporated to made large vacuoles Fig.

Glomerular capillary endothelial cells and glomerular basement membrane were shown in normal histological structures. Group 6 treated with Abelcet for 28 days: In proximal tubule epithelial cells, vacuolar structures were increased prominently. These cells were rich of mitochondria and lysosomes. The spherical and elongated mitochondria were abundant.

There was an increase in the spaces between the interdigitations Fig. In distal tubule epithelial cells, nucleus and the organelles were shown in normal ultrastructure Fig. In glomerular capillary endothelial cells and glomerular basement membrane were shown in normal histological properties. Control groups, normal proximal convoluted tubule. Control group, normal glomerulus are seen. Group 2, proximal convoluted tubule are seen normal as in control groups.

Ahfotericina 2, distal anfotrricina are seen normal. Nucleus Nmitochondria M. In this paper, the renal toxicity profiles of liposomal Amphotericin B Ambisome and Amphotericin B lipid complex Abelcet administrating following short and long time periods have been described in experimental animals.

The results of these experiments indicate that, both drug administrations cause some morphological changes in the distal and proximal convoluted tubule cells in rats.

Classical amphotericin B has disrupted the function of tubular and vascular smooth muscle cells by changing the permeability of cell membranes and leads to various tubular transport defects and vasoconstriction on blood vessels Doubek et al. It has been established that lipid based amphotericin B is responsible from transforming cell morphology, function and intracellular transport system by the toxic effect of the amphotericin B molecule Doubek et al.

In our study, the distribution, size and shape of mitochondria, basal lamina and glomerulus were seen normal both in proximal and distal tubular cells after short and long-term administration of Ambisome Figs. They indicate that despite the severe morphological tubular damage, the glomerular defect is functional.

In addition, it was determined that tubular destruction in the cell cytoplasm with small vacuolar structures and an increase in densities of peroxisomes Doubek et al. In our experiments as well as glomerular structures and basement membrane were seen normal in both drugs after 14 and 28 day usage as like in control groups Fig.

However, some morphological changes on apical cytoplasm like lots number of lysosomes, lytic areas and vacuolar structures in tubuler epithelium in rat kidneys have been shown after in short-term use of Abelcet Figs. By the way, rats receiving short-term Ambisome showed near normal tubular cells Figs. On the other hand after long-term Ambisome and Abelcet administration vacuolar structure has been shown increased Figs.

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It is thought that this vacuolar structure considered due to additional dilatations of endoplasmic reticulum in kidney tubule cells Mihatsch et al. Basal folding into the lumen has been shown also increased after long term usage of both drug administrations. Moreover, some of the cells made protrusion into the lumen Figs. Since, amphotericin B alters the transport system of cell membranes, it can be speculated that the basal folding may represent an increase in the surface area of the basal plasma membranes for the enhancement of the membrane transport of the proximal tubule cells Sawaya et al.

If a cell exposed to a toxic substance; harmful substances accumulate in the cell and breaks down the cell metabolism. It is known that, all of these harmful substances which are accumulated in cytoplasm are a result of luposomal of the organelles. These harmful substances are removing lkposomal the cell by lysosomes function. So we think that lysosomal structures which are seen in the proximal and distal tubule cells in our investigation are developed due to the effect afotericina amphoterisin B incorporated with lipids, like ambisome and abelcet.

When morphological findings in this paper are taken into consideration, the cell degeneration seen with ambisome using seems to be less severe compared to abelcet using. Anfoterickna, in our study it was indicated that, after short-term ambisome treatment proximal and distal tubule epithelial cells, nuclei and organelles were observed in normal structure.

However, only changes were observed in proximal tubule cells in Abelcet group Fig. After long-term treatment, vacuolar and lysosomal structures were increased in only proximal tubule cells in abelcet group, but in long term using Ambisome, some morphologic changes were observed in proximal and distal tubules Figs. The differences observed in proximal tubule were significantly higher than distal tubules. It can be assumed, that proximal tubule epithelial cells were more sensitive to both formulas than the distal tubule cells.

According to these data, it could be thought that lipid formulations of amphotericin B might change the kidney function due to amphotericin B molecule’s acute effect. In summary, the main ultrastructural findings were vacuolization and increasing lysosomes in tubular cells in Abelcet using at short and long time and only after long time use of Ambisome.

Liposomal Amphotericin B and Leishmaniasis: Dose and Response

Anfoteridina, our findings pointed out the risk of increased morphological changes due to short-long term use of the lipid based amphotericin B antifungal agent, Abelcet and long term use of Ambisome. In conclusion, although lipid based amphotericin B agents are effective in invasive fungal infection management, their toxic effects should be kept in mind during long-term usage.

Group 3, proximal convoluted tubule. Lytic areas asterix are seen. Vacuoles Vlysosomes Lbrush border BB. Group anfotwricina, proximal convoluted tubule. Cytoplasmic protrusion arrowdeep basal folding asterix are striking. Nucleus Nlysosomes L. Cytoplasmic part contained nucleus N and vacuoles V are made protrusion between microvilli Mv. Group 5, distal convoluted tubule. Increased vacuoles V and deep foldings asterix are noticed. Group 6, proximal convoluted tubule.

Increased vacuoles Vlysosomes Lmitochondria M and deep foldings asterix are seen. Group 6, distal convoluted tubule is seen normal appearance.

Nucleus N and mitochondria M.