Effects of pomegranate seed oil on lower-extremity ischemia–reperfusion damage: Insights into oxidative stress, inflammation, and cell death

Lower-extremity ischemia–reperfusion (IR) injury causes oxidative stress, inflammation, and cell death. Pomegranate seed oil (PSO) contains polyphenols with antioxidant and anti-inflammatory properties that may protect against IR injury. In this single-center, randomized, double-blind trial, 60 patients undergoing reperfusion for lower-limb ischemia were allocated to four arms: Control (n = 15), IR + placebo (n = 20), IR + PSO low dose (n = 10), and IR + PSO high dose (n = 15). Muscle biopsies of the gastrocnemius were obtained at baseline and 72 h after reperfusion. The primary endpoint was total histological injury score. The secondary outcomes included total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index, tumor necrosis factor-alpha, interleukin-6, caspase-3, and cytochrome-C. PSO significantly reduced histological injury: Median total injury score was 9 (7–11) in IR, 6 (4–8) in IR + PSO low, and 3 (2–5) in IR + PSO high (P < 0.001). TOS was lower and TAS higher in PSO groups (TOS: IR – 26.36 ± 9.18 µmol/L vs. IR + PSO high – 8.14 ± 3.40 µmol/L, TAS: IR – 0.63 ± 0.05 mmol/L vs. IR + PSO high – 1.12 ± 0.32 mmol/L). Multivariable logistic regression showed that PSO treatment was associated with lower odds of severe IR injury (odds ratio: 0.40, 95% confidence interval: 0.18–0.90). In this exploratory study, PSO supplementation was associated with reduced histological and biochemical markers of IR injury, with greater effects at higher dose. Larger, registered randomized trials are required to confirm efficacy, optimal dosing, and safety.