Comparative effects of silibinin and deferoxamine on skeletal muscle injury and regeneration in a rat model of compartment syndrome

Compartment syndrome (CS) causes ischaemia–reperfusion-related skeletal muscle injury, and adjunct pharmacological strategies may reduce secondary tissue damage. This study compared silibinin and deferoxamine in a rat model of CS. Thirty-six male Sprague–Dawley rats were randomised into six groups ( n = 6). CS was induced by applying 140 mmHg external cuff pressure to the right hind limb for 3 h, followed by reperfusion. Animals received vehicle, silibinin (200 mg/kg/day by oral gavage), or deferoxamine (100 mg/kg/day intraperitoneally) until Day 4 or Day 14. CS + vehicle rats received oral distilled water and intraperitoneal 0.9% NaCl without active drug; active treatment groups received route-matched vehicle through the alternative route. Functional performance was assessed using the inclined plane test, and gastrocnemius muscles were examined using hematoxylin-eosin, Masson’s trichrome, Pax7, and Myogenin staining. At Day 14, both treatment groups showed higher inclined plane performance and lower myofiber necrosis and collagen-associated remodeling scores than the CS + vehicle group. Pax7 and Myogenin showed distinct patterns of expression between the Day 4 and Day 14 cohorts. Overall, silibinin and deferoxamine were associated with lower histopathological injury and higher functional performance in the Day 14 groups than in the corresponding Day 4 groups in this experimental CS model, while Pax7 and Myogenin findings indicated differences in myogenic marker expression between the Day 4 and Day 14 cohorts rather than definitive regenerative kinetics.