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Updated: Aug 13, 2025
Preparation and In Vitro Characterization of Dendrimer-based Contrast Agents for Magnetic Resonance Imaging
Published on: December 4, 2016
Comparison of linear versus macrocyclic gadolinium chelates in rat skeletal muscle
Mehmet Sabri Balik1, Fatma Beyazal Celiker2, Levent Tumkaya3
1Department of Orthopedics and Traumatology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkiye.
Objective:
We investigated the effects on skeletal muscle of gadolinium based linear and macrocyclic radiocontrast agents applied at experimental intervals using histopathological methods.
Methods:
Thirty-two male Sprague-Dawley rats were included in the study for histopathological analysis. No procedure was performed on the healthy control group. The sham group received 0.1 ml/kg intravenous (IV) saline solution through the tail vein 4 times weekly for 5 weeks. The gadodiamide group received total 2 mmol/kg IV gadodiamide through the tail vein 4 times weekly for 5 weeks. The gadoteric-acid group received 2 mmol/kg IV gadoteric acid through the tail vein 4 times weekly for 5 weeks.
Results:
We determined no marked apoptotic myofibrils associated withcaspase-3 expression in these two groups. Furthermore, no calcineurin expression was observed in myofibrils in the two groups. However, quantitative analyses revealed a decrease in muscle-fiber area in the gadodiamide and gadoteric-acid groups compared to the control group (Respectively; p=0.001 and p=0.017).
Conclusion:
In our experimental study, linear and macrocyclic GBCAs applied at repeated doses played no role in myofibril damage induced by caspase-3 and calcineurin - nuclear factor of activated T-cells in skeletal muscle tissue.
Insights
Repeated doses of linear and macrocyclic gadolinium-based contrast agents (GBCAs) did not cause myofibril damage in rats. However, these agents did lead to a decrease in skeletal muscle fiber area, indicating potential subtle effects.
Area of Science:
- Biomedical Science
- Histopathology
- Radiology
Background:
- Gadolinium-based contrast agents (GBCAs) are widely used in medical imaging.
- Concerns exist regarding the long-term effects of GBCAs, particularly linear and macrocyclic agents, on various tissues.
- Skeletal muscle effects of repeated GBCA administration are not fully understood.
Purpose of the Study:
- To investigate the histopathological effects of linear and macrocyclic GBCAs on skeletal muscle tissue.
- To evaluate the potential for myofibril damage and cellular changes induced by repeated GBCA exposure.
- To assess the role of caspase-3 and calcineurin pathways in GBCA-induced skeletal muscle alterations.
Main Methods:
- Histopathological analysis was performed on Sprague-Dawley rats exposed to gadodiamide or gadoteric acid.
- Rats received intravenous GBCAs (2 mmol/kg) or saline (sham) four times weekly for five weeks.
- Control groups included healthy animals with no procedures.
Main Results:
- No significant apoptotic myofibrils or caspase-3 expression were observed in GBCA-treated groups.
- Calcineurin expression was not detected in myofibrils of treated or control groups.
- Quantitative analysis revealed a statistically significant decrease in muscle fiber area in both gadodiamide and gadoteric acid groups compared to controls (p=0.001 and p=0.017, respectively).
Conclusions:
- Repeated administration of linear and macrocyclic GBCAs does not induce myofibril damage via caspase-3 or calcineurin pathways in skeletal muscle.
- Despite the absence of direct myofibril damage, GBCAs were associated with a reduction in skeletal muscle fiber size.
- Further research is warranted to elucidate the mechanisms behind the observed decrease in muscle fiber area.
