In-vivo antioxidant and therapeutic effects of ellagic acid on ischemia-reperfusion injury in skeletal muscle

Aim: Skeletal muscle ischemia-reperfusion (IR) injury is a critical clinical issue characterized by oxidative stress, inflammation, and tissue damage, potentially leading to systemic organ dysfunction. Ellagic acid (EA), a naturally occurring polyphenolic compound, is widely recognized for its strong antioxidative, anti-inflammatory, and antiapoptotic effects demonstrated in various preclinical studies. This study sought to assess the therapeutic effects of EA in a rat model of lower extremity IR injury, focusing on histopathological and biochemical parameters. Material and Methods: 24 male Albino Wistar rats were randomly divided into four groups: Sham, EA, IR, and IR+EA. IR injury was induced by occluding the infrarenal abdominal aorta for 45 minutes, followed by 120 minutes of reperfusion. EA (40 mg/kg) was administered intraperitoneally prior to reperfusion. Left gastrocnemius muscle samples were collected for histopathological and biochemical analyses, including TOS, TAS, OSI, levels and PON-1 enzyme activity. Results: The IR group showed marked muscle injury, with a significantly higher total injury score (10.00±0.63) compared to the Sham (2.00±0.58) and EA groups (2.00±0.52) (p<0.001, both). The IR-EA group demonstrated notable improvement, with a reduced total injury score (6.17±0.54), which was also significantly lower than the IR group (p<0.001). Biochemically, TAS levels and PON-1 activity significantly decreased while TOS and OSI levels increased in the IR group compared to the sham and EA groups. In addition, EA treatment significantly increased TAS levels and PON-1 activity while reducing TOS and OSI levels in the IR-EA group compared to the IR group (p=0.039, p=0.045, p=0.045, p=0.007, respectively). Conclusion: EA effectively mitigated skeletal muscle damage induced by IR injury through its antioxidative, anti-inflammatory, and antiapoptotic mechanisms. The results suggest that EA exhibits potential effects as a therapeutic agent in managing IR-related injuries.