Related Experiment Videos
Cyclodextrin nephrosis in the rat
Abstract:
The renal toxicity of the Schardinger dextrins, alpha and beta-cyclodextrin, is manifested as a series of alterations in the vacuolar organelles of the proximal convoluted tubule. These changes begin as an increase of apical vacuoles and the appearance of giant lysosomes. The giant lysosomes characteristic of cyclodextrin nephrosis are notable because of the prominent acicular microcrystals embedded in the lysosomal matrix. Giant vacuoles devoid of acid phosphatase reaction product are found in advanced lesions. The vacuolar apparatus shows advanced changes prior to manifestation of lesions in mitochondria and other organelles. These observations indicate a role of the vacuologenic apparatus in the nephrotic process. Intracellular concentration of toxin via the lysosomal pathway represents a perversion of the physiologic function of the proximal tubule which ultimately leads to cell death.
Insights
Schardinger dextrins, like alpha and beta-cyclodextrin, cause kidney toxicity by damaging vacuolar organelles in proximal tubules. This leads to giant lysosomes and cell death, highlighting the vacuolar apparatus
Area of Science:
- Nephrology
- Toxicology
- Cell Biology
Background:
- Schardinger dextrins, including alpha- and beta-cyclodextrins, are known to induce renal toxicity.
- The proximal convoluted tubule is the primary site of observed toxic alterations.
- Vacuolar organelles are implicated in the mechanism of cyclodextrin-induced nephropathy.
Purpose of the Study:
- To investigate the specific alterations in vacuolar organelles induced by Schardinger dextrins in the proximal convoluted tubule.
- To elucidate the role of the vacuolar apparatus in the pathogenesis of cyclodextrin nephrosis.
- To understand the cellular mechanisms underlying cyclodextrin toxicity in renal cells.
Main Methods:
- Light microscopy was used to observe cellular changes in the proximal convoluted tubule.
- Histochemical staining was employed to assess the activity of acid phosphatase within lysosomes.
- Ultrastructural analysis was performed to examine the morphology of organelles, including vacuoles, lysosomes, and mitochondria.
Main Results:
- Increased apical vacuoles and the formation of giant lysosomes containing acicular microcrystals were observed.
- Advanced lesions showed giant vacuoles devoid of acid phosphatase activity.
- Significant changes in the vacuolar apparatus preceded damage to mitochondria and other organelles.
Conclusions:
- The vacuolar apparatus plays a critical role in the development of cyclodextrin nephrosis.
- Intracellular accumulation of cyclodextrins via the lysosomal pathway represents a toxic mechanism.
- This process disrupts normal proximal tubule function, ultimately leading to cell death.