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Ultrastructural changes in skeletal muscles of rats treated neonatally with 6-mercaptopurine
Insights
This study examined muscle damage in young rats treated with 6-mercaptopurine monohydrate (6-MP). 6-MP caused early muscle fiber disorganization, primarily affecting Z-bands and myofibrils.
Area of Science:
- Muscle physiology
- Toxicology
- Developmental biology
Background:
- 6-mercaptopurine monohydrate (6-MP) is an immunosuppressant drug.
- Understanding drug-induced myopathy is crucial for patient safety.
- Early developmental stages may exhibit unique sensitivities to xenobiotics.
Purpose of the Study:
- To investigate the ultrastructural muscle changes in young rats exposed to 6-mercaptopurine monohydrate.
- To determine the onset and progression of 6-MP-induced myopathy during early development.
Main Methods:
- Rats (2- and 6-month-old) were administered 6-mercaptopurine monohydrate (2 mg base/kg) daily from 2 to 22 days of age.
- Muscle tissue was analyzed using electron microscopy to identify ultrastructural alterations.
Main Results:
- Subsarcolemmal alterations, including Z-band disorganization and myofibril loss, were observed early.
- Extensive lesions showed complete fiber involvement with vacuoles within disorganized fibrils.
- Peripheral nerves and blood vessels remained unaffected, indicating a primary muscle pathology.
Conclusions:
- 6-mercaptopurine monohydrate induces significant ultrastructural changes in developing rat muscles.
- The observed myopathy is primarily myogenic, originating within the muscle fibers themselves.
- These findings highlight the potential for 6-MP to cause muscle toxicity during early life stages.
Abstract:
The purpose of this study was to characterize the ultrastructural changes in the muscles of 2- and 6-month-old rats that were injected with 6-mercaptopurine monohydrate (6-MP) at 2 mg base/kg sc daily from 2 to 22 days of age. The earliest, usually subsarcolemmal alterations, were disorganization of fibrils at the Z-bands with excessive Z-band-like material and loss of myofibrils. In the most extensive lesions, the entire fiber was involved, with vacuoles within the disorganized fibrils. The peripheral nerves and vessels were unremarkable. Thus 6-MP-induced changes appear to be primarily myogenic in origin.