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Updated: Jun 19, 2025
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Daprodustat reduces skeletal muscle ischemia-reperfusion injury in mice
Weiqiang Wu1,2,3,4, Yongfa Zhang1,4,5, Ying Zhang6
1Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Purpose:
The purpose of the present work was to assess the specific effects and underlying mechanisms of Daprodustat (GSK1278863) on skeletal muscle injury induced by ischemia reperfusion (I/R).
Methods:
C57BL/6 mice were randomized into the skeletal muscle I/R injury (I/R), Daprodustat (GSK1278863) pretreatment and I/R (I/R + GSK) and sham operation (Sham) groups. The skeletal muscle I/R injury model was established by placing an orthodontic rubber band at the left hip joint for 3 h and releasing it for 3 h. H&E staining, wet weight/dry weight ratio assessment, TUNEL assay, ELISA, qRT-PCR and immunoblot were utilized to assess the effects of Daprodustat.
Results:
Daprodustat pretreatment significantly ameliorated apoptosis in skeletal muscle cells, reduced oxidative damage and suppressed inflammatory cytokines. Mechanistically, Daprodustat positively affected NF-κB signaling activation.
Conclusion:
These data demonstrated that Daprodustat may provide a potential clinical approach for preventing or treating skeletal muscle injury induced by I/R.
Insights
Daprodustat effectively protects against skeletal muscle ischemia reperfusion (I/R) injury by reducing cell death, oxidative damage, and inflammation. This drug shows promise for clinical use in preventing and treating I/R-induced muscle damage.
Area of Science:
- Biomedical Sciences
- Skeletal Muscle Physiology
- Pharmacology
Background:
- Ischemia reperfusion (I/R) injury is a significant cause of skeletal muscle damage.
- Understanding protective mechanisms against I/R injury is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the protective effects of Daprodustat (GSK1278863) on skeletal muscle I/R injury.
- To elucidate the underlying mechanisms by which Daprodustat mitigates I/R-induced damage.
Main Methods:
- A mouse model of skeletal muscle I/R injury was established.
- Mice were pretreated with Daprodustat before inducing I/R.
- Histological analysis (H&E), cell apoptosis (TUNEL assay), oxidative stress markers, inflammatory cytokine levels (ELISA), and signaling pathway activation (qRT-PCR, immunoblot) were assessed.
Main Results:
- Daprodustat pretreatment significantly reduced apoptosis in skeletal muscle cells.
- The drug decreased oxidative damage and suppressed inflammatory cytokine release.
- Daprodustat positively modulated NF-κB signaling pathway activation.
Conclusions:
- Daprodustat demonstrates significant protective effects against skeletal muscle I/R injury.
- The drug's mechanism involves reducing apoptosis, oxidative stress, and inflammation, partly through NF-κB signaling.
- Daprodustat represents a potential therapeutic agent for preventing or treating I/R-induced skeletal muscle injury.
