Curcumin and aerobic training mitigate cadmium-induced oxidative stress and apoptosis via miR-21 and miR-133 modulation in the rat hippocampus.

Introduction: This study investigated the eight-week concomitant effects of aerobic training (AT) and curcumin (Cu) supplementation on the oxidant-antioxidant pathway and apoptosis in the hippocampus of cadmium (Cd)-exposed male Wistar rats, specifically focusing on miR-21 and miR-133.

Methods: Forty male Wistar rats were randomly assigned to five groups (n=8 per group): 1) Control ©, 2) Cadmium (Cd), 3) Cd+Cu, 4) Cd+AT, and 5) Cd+Cu+AT. Groups 2-5 received 5 mg/kg/day of cadmium via drinking water. AT groups engaged in an 8-week aerobic exercise regimen, five sessions per week. Furthermore, groups 3 and 5 received 160 µL/kg/day of curcumin orally.

Results: Cd exposure significantly disrupted the oxidant-antioxidant balance (decreased SOD and GPx, increased MDA; all p < 0.001) and elevated the Bax/BCL-2 ratio (p < 0.001). The combination of AT and Cu markedly counteracted these effects; SOD and GPx levels significantly increased, while MDA showed a significant decrease (p < 0.001). Moreover, this combined intervention notably reduced P53 expression and the Bax/BCL-2 ratio (both p < 0.001), demonstrating a robust protective effect against cadmium toxicity. Importantly, regarding microRNAs, the Cd+AT+Cu group exhibited a significant reduction in miR-21 and a significant increase in miR-133 compared to the Cd group (both p < 0.01).

Conclusion: Both aerobic training and curcumin alleviated cadmium-induced oxidative stress and apoptosis. Curcumin alone demonstrated a more pronounced effect than aerobic training. However, the combined intervention of aerobic training and curcumin exhibited remarkable synergistic effects, significantly improving antioxidant status and reducing apoptosis compared to individual treatments and cadmium exposure alone.