Comprehensive evaluation of the antioxidant, anti-inflammatory, and anti-apoptotic effects of hydroxytyrosol in skeletal muscle ischemia–reperfusion injury
TL;DR
Hydroxytyrosol exerted significant protective effects against skeletal muscle I/R injury by attenuating oxidative stress, suppressing inflammatory mediators, and reducing apoptosis.
Abstract
Background
Skeletal muscle ischemia–reperfusion (I/R) injury is a complex pathological process characterized by excessive reactive oxygen species production, activation of inflammatory cascades, and apoptosis, ultimately resulting in substantial structural and functional tissue damage. Hydroxytyrosol (HT), a naturally occurring phenolic compound predominantly in olive-derived products, exhibits potent antioxidant and anti-inflammatory properties. This study aimed to comprehensively evaluate the potential protective effects of HT against lower-extremity skeletal muscle I/R injury in an experimental rat model.
Methods
Twenty-four adult Wistar albino rats were randomly assigned to four experimental groups: Sham, HT-Control, I/R, and HT+I/R. Hind-limb ischemia was induced for two hours, followed by two hours of reperfusion. In the treatment group, HT (10 mg/kg, intraperitoneally) was administered 30 minutes before ischemia induction. Serum oxidative stress parameters, including total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), were measured. Skeletal muscle tissues were evaluated histopathologically, and interleukin-1β (IL-1β) levels, caspase-3 expression, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells were assessed.
Results
Compared with the Sham group, the untreated I/R group exhibited significantly higher TOS and OSI levels, increased histopathological injury scores, marked inflammatory cell infiltration, and enhanced apoptotic activity (p<0.05). HT administration significantly attenuated oxidative stress, reduced inflammatory responses, decreased tissue injury severity, and lowered apoptotic indices compared with the I/R group (p<0.05).
Conclusion
Hydroxytyrosol exerted significant protective effects against skeletal muscle I/R injury by attenuating oxidative stress, suppressing inflammatory mediators, and reducing apoptosis. These findings highlight the therapeutic potential of HT as a promising adjunctive strategy in the prevention and management of ischemia–reperfusion-induced tissue damage.