Modulatory effects of 6-Gingerol on erythrocyte deformability and morphology following lower extremity skeletal muscle ischemia-reperfusion injury in rats.

Oxidative stress from ischemia-reperfusion (IR) injury severely compromises erythrocyte deformability, a critical factor that disrupts microvascular flow and thereby exacerbates reperfusion injury. This study provides a novel perspective by directly investigating the protective effects of 6-Gingerol, known for its potent antioxidant properties, on erythrocyte function in a rat model of lower-extremity skeletal muscle IR. Twenty-four Wistar albino rats were divided into four groups: Sham (n = 6), DMSO (n = 6), IR (n = 6), and 6-Gingerol-IR (6G-IR, n = 6, 6 mg/kg i.p., 1 h before ischemia). Ninety minutes of ischemia were followed by 90 min of reperfusion. Compared to the IR group, the 6G-IR group exhibited a significant improvement in erythrocyte deformability (Rrel 2.13 ± 0.36 vs. 3.29 ± 0.40; p = 0.002, Cohen’s d = 3.9), a substantial reduction in lipid peroxidation (MDA 16.23 ± 2.11 vs. 22.14 ± 5.78 nmol/ml; p = 0.002, Cohen’s d = 1.3), and an apparent increase in antioxidant capacity (SOD 11.36 ± 2.25 vs. 6.93 ± 2.54 U/ml; p < 0.001, Cohen’s d = 2.0). Furthermore, 6G-IR significantly attenuated morphological damage (MGG score) and suppressed eNOS expression (H-score) compared to the IR group (Cohen’s d = 1.7 and d = 1.4, respectively). These findings provide strong preliminary evidence that 6-Gingerol preserves microcirculatory function through SOD-mediated neutralization of superoxide, thereby preventing peroxynitrite-induced erythrocyte membrane damage. Further power-calculated studies are warranted to explore its clinical translational potential.