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Ultrastructural examinations of rat myocardium on low-magnesium diet during administration of methotrexate
1Cell Pathophysiology Department, Medical Centre of Postgraduate Education, Warszawa, Poland.
Abstract:
Methotrexate administration intraperitoneally in doses of 1 mg/kg body weight twice weekly for six weeks produced in the myocardial fibres of these animals slight focal lesions from the third week of the experiment on with the appearance of isolated giant mitochondria of bizarre shapes with electron-dense membranes containing granules, or groups of mitochondria with swollen matrix and disintegration or, partial breakdown of mitochondrial cristae, numerous lysosomes and less numerous autophagosomes, considerable lysis of myofibrils and myofilaments, widening of the tubules of the sarcoplasmic reticulum and T-tubules, presence of few fat droplets, widening of intercalated discs, rarely cytoplasm swelling. From the fifth week on foci of cardiomyocyte fibrosis, in some places swelling of vascular endothelial cells, and a very considerable rise in the number of collagen cells in extracellular spaces. Simultaneous low-magnesium diet and methotrexate caused earlier, from the second week on, and greater intensity of focal necrotic and degenerative changes of cardiomyocytes.
Insights
Methotrexate causes myocardial damage, including mitochondrial and myofibril changes, fibrosis, and cardiomyocyte necrosis. A low-magnesium diet exacerbates these methotrexate-induced cardiac effects.
Area of Science:
- Cardiovascular Pathology
- Toxicology
- Cell Biology
Background:
- Methotrexate (MTX) is a widely used chemotherapy agent.
- Cardiotoxicity is a known, albeit less common, side effect of MTX therapy.
- Understanding the cellular mechanisms of MTX-induced myocardial injury is crucial for patient management.
Purpose of the Study:
- To investigate the ultrastructural cardiac changes induced by intraperitoneal methotrexate administration.
- To evaluate the impact of a simultaneous low-magnesium diet on methotrexate-induced cardiotoxicity.
Main Methods:
- Adult animals received intraperitoneal methotrexate (1 mg/kg) twice weekly for six weeks.
- Histopathological and ultrastructural analyses were performed on myocardial tissues.
- A subset of animals was maintained on a low-magnesium diet concurrently with methotrexate treatment.
Main Results:
- Methotrexate induced focal myocardial lesions starting from week 3, characterized by mitochondrial abnormalities (giant mitochondria, matrix swelling, cristae disintegration), increased lysosomes, myofibril lysis, sarcoplasmic reticulum dilation, and widened intercalated discs.
- From week 5, cardiomyocyte fibrosis, vascular endothelial cell swelling, and increased extracellular collagen were observed.
- Concurrent low-magnesium diet accelerated and intensified these necrotic and degenerative changes, evident from week 2.
Conclusions:
- Intraperitoneal methotrexate administration causes significant ultrastructural damage to cardiomyocytes.
- A low-magnesium diet potentiates methotrexate-induced cardiotoxicity, leading to earlier and more severe myocardial degeneration.
- These findings highlight the importance of monitoring cardiac health and nutritional status in patients receiving methotrexate.