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Acrylic microspheres in vivo VII: morphological studies on mice and cultured macrophages
Abstract:
Intravenously injected microparticles of polyacrylamide were cleared from the circulatory system in mice predominantly in liver, spleen, and bone marrow in mice by macrophages belonging to the reticuloendothelial system. In these cells, particles were found in dilated secondary lysosomes. The lysosomotropic character of the particles was further demonstrated using cultured peritoneal mouse macrophages. Histological changes of the liver, spleen, and bone marrow detectable by light and electron microscopy could only be seen after administration of massive doses of microparticles corresponding to 160 mg/kg body weight. In such cases, a medium-coarse vacuolization of liver parenchymal cells could be seen 1-2 days after particle administration. After 3-5 days, degeneration and necrotic cellular alteration occurred in the liver, spleen, and bone marrow. One week after particle administration, regeneration started under formation of granulomas which replaced the necrotic areas. The tissues later became normalized (after 2-3 weeks), but small granulomas remained for several weeks. The damage was parallelled by changes in the liver and spleen weights. Electron microscopy of the liver revealed that the initiated vacuolization of the parenchymal cells was due to mitochondrial swelling with rupture of the mitochondrial cristae.
Insights
Polyacrylamide microparticles injected into mice are cleared by the reticuloendothelial system, primarily in the liver, spleen, and bone marrow. High doses cause temporary tissue damage and inflammation, followed by regeneration and normalization.
Area of Science:
- Biomaterials Science
- Toxicology
- Immunology
Background:
- Polyacrylamide microparticles are used in various biomedical applications.
- Understanding their in vivo fate and potential toxicity is crucial for safety assessment.
Purpose of the Study:
- To investigate the biodistribution, cellular uptake, and potential toxicity of intravenously injected polyacrylamide microparticles in mice.
- To elucidate the mechanisms underlying microparticle-induced tissue alterations.
Main Methods:
- Intravenous injection of polyacrylamide microparticles in mice.
- Analysis of tissue distribution (liver, spleen, bone marrow) using light and electron microscopy.
- Assessment of cellular uptake by macrophages and lysosomal localization.
- Evaluation of histological changes and organ weights post-administration.
Main Results:
- Microparticles were predominantly cleared by macrophages of the reticuloendothelial system in the liver, spleen, and bone marrow.
- Particles localized within secondary lysosomes.
- Massive doses (160 mg/kg) induced reversible vacuolization, degeneration, and necrosis in target organs.
- Mitochondrial swelling and cristae rupture were observed in liver parenchymal cells.
- Regeneration and granuloma formation occurred, with eventual tissue normalization.
Conclusions:
- Polyacrylamide microparticles are efficiently cleared by the reticuloendothelial system.
- High doses can cause transient, dose-dependent organ toxicity, primarily affecting mitochondria.
- The observed effects are reversible, with regeneration occurring after initial damage.