The Effect of Aerobic Training with Curcumin on Liver Necroptosis of Rats Exposed to Cadmium: A Randomized Trial

Background: Necroptosis-related diseases can be triggered by environmental heavy metal pollutants. Objectives: In the present study, we investigated whether aerobic training (AT) combined with curcumin (Cu) could mitigate liver necroptosis in rats exposed to cadmium (Cd) by regulating RIPK1, RIPK3, and MLKL expression. Methods: Forty male Wistar rats aged 8 - 10 weeks (n = 8 in each group) were randomly allocated into five groups: Control (C), Cd, Cd + Cu, Cd + AT, and Cd + Cu + AT. The Cd groups received 5 mg/kg of Cd daily via drinking water. The AT groups underwent running sessions for eight weeks, five times per week, with each session lasting 30 - 60 minutes at a speed of 15 m/min on a 15-degree incline. Additionally, the daily intake of Cu was 160 µL/kg administered orally. Results: The expression of RIPK1, RIPK3, and MLKL was significantly decreased in the Cd + Cu, Cd + AT, and Cd + Cu + AT groups compared to the Cd group. The expression of RIPK1 and MLKL was significantly decreased in the Cd + Cu + AT group compared to the Cd + Cu and Cd + AT groups. SIRT1 expression was significantly increased in the Cd + Cu and Cd + AT groups compared to the Cd group; and in the Cd + Cu + AT group compared to the Cd + Cu and Cd + AT groups (P < 0.05). Conclusions: Exposure to Cd was linked with heightened markers of necroptosis. However, AT and Cu attenuated Cd-induced liver necroptosis by reducing the expression of MLKL, RIPK1, and RIPK3 while enhancing SIRT1 expression. The combination of AT and Cu showed superior effects.