Metabolic Status Modulates Erythrocyte Antioxidant Enzyme Responses to Selected Phytochemicals: An Ex Vivo Study

Background: Oxidative stress plays an important role in the development and progression of prediabetes (PD) and type 2 diabetes mellitus (T2DM). Since metabolic disturbances may alter the functional properties of erythrocyte antioxidant systems, we hypothesised that erythrocyte antioxidant enzymes would exhibit differential responses to phytochemical exposure depending on metabolic status. Therefore, this ex vivo study compared the responses of erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) to selected phytochemicals in healthy individuals, subjects with PD, and patients with T2DM. Methods: Erythrocyte hemolysates collected from healthy controls (CG), individuals with PD (PDG), and T2DM (T2DMG) were incubated with curcumin, resveratrol, fisetin, and cinnamon extract. The activities of SOD, CAT, and GPx were determined spectrophotometrically. Statistical analyses included a Kruskal–Wallis test, Friedman ANOVA and a Spearman rank correlation coefficient. For significant results, post hoc tests were performed with Benjamini–Hochberg correction for multiple comparisons. Results: Baseline (vehicle control) SOD activity was significantly lower in T2DMG and PDG compared with CG (p = 0.0035). SOD activity was higher following incubation with curcumin in T2DMG and CG (p < 0.05), while resveratrol showed a significant effect only in CG (p = 0.0326). Cinnamon extract increased CAT activity, particularly in CG (p = 0.0169). Among the analysed enzymes, GPx exhibited the highest responsiveness to phytochemical exposure. Curcumin and fisetin increased GPx activity in PDG and T2DMG, while cinnamon extract improved activity in all groups (p < 0.05). Additionally, baseline GPx activity was negatively correlated with body weight (q = 0.0127) and body mass index (q = 0.0260). Conclusions: These findings suggest that metabolic status influences the responsiveness of erythrocyte antioxidant enzymes to phytochemical exposure. While the tested compounds exerted direct effects on antioxidant enzyme activities, the magnitude and pattern of these responses differed between healthy, prediabetic, and T2DM individuals. This suggests that alterations associated with metabolic dysfunction may influence erythrocyte antioxidant defence mechanisms and their responsiveness to bioactive compounds. These observations provide a rationale for further in vivo and clinical studies addressing the interaction between metabolic status and phytochemical-mediated antioxidant effects.