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Early changes in chlorphentermine myopathy of rat studied by freeze fracturing
Abstract:
Chlorphentermine interferes with the metabolism of phospholipids. When administered to the rat in daily doses for 5 days, it causes necrosis of muscle fibers that are rich in mitochondria. Before the onset of necrosis, the following characteristics of freeze-fractured muscle preparations were observed: multilayered lipid globules and single-layered lipid membranes without membrane particles; different stages of exocytosis of lipid through the plasma membrane of the muscle fibers; and areas of plasma membrane that were devoid of particles of intramembranous proteins. These latter areas may arise secondary to exocytosis, to fusion of lipid vesicles with the plasma membrane, or to a direct action of chlorphentermine on the membrane. It is not known whether these areas give rise to membrane defects and fiber necrosis.
Insights
Chlorphentermine disrupts phospholipid metabolism, leading to muscle fiber necrosis in rats. This involves lipid changes and membrane alterations in mitochondria-rich muscle cells.
Area of Science:
- Biochemistry
- Cell Biology
- Toxicology
Background:
- Phospholipids are crucial components of cell membranes.
- Muscle fibers, particularly those rich in mitochondria, have specific metabolic demands.
- Chlorphentermine is a drug with known metabolic effects.
Purpose of the Study:
- To investigate the effects of chlorphentermine on muscle fiber metabolism.
- To identify ultrastructural changes in muscle fibers preceding necrosis induced by chlorphentermine.
Main Methods:
- Rats were administered daily doses of chlorphentermine for 5 days.
- Freeze-fracture electron microscopy was used to examine muscle preparations.
- Ultrastructural analysis focused on lipid metabolism and plasma membrane integrity.
Main Results:
- Chlorphentermine administration led to necrosis of mitochondria-rich muscle fibers.
- Pre-necrotic changes included multilayered lipid globules and particle-less lipid membranes.
- Observed were stages of lipid exocytosis and areas of plasma membrane devoid of intramembranous proteins.
Conclusions:
- Chlorphentermine interferes with phospholipid metabolism, impacting muscle fiber integrity.
- Observed membrane alterations, including lipid exocytosis and particle-deficient areas, may precede muscle fiber necrosis.
- The precise mechanism linking these membrane changes to necrosis requires further investigation.