AMPK/PPAR-γ/NF-κB axis participates in ROS-mediated apoptosis and autophagy caused by cadmium in pig liver

The experiment was conducted to investigate the effects of Cadmium (Cd) on growth performance, blood biochemical parameters, oxidative stress, hepatocyte apoptosis and autophagy of weaned piglets. A total of 12 healthy weaned piglets were randomly assigned to the control and the Cd group, which were fed with a basal diet and the basal diet supplemented with 15 ± 0.242 mg/kg CdCl2 for 30 d, respectively. Our results demonstrated that Cd significantly decreased final body weight, average daily feed intake (ADFI), average daily gain (ADG) and increased feed-to-gain (F/G) ratio (P < 0.05). For blood biochemical parameters, Cd treatment significantly decreased the red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), total protein, albumin, copper content and iron content (P < 0.05). In addition, liver injury was observed in the Cd-exposed group. Our results also demonstrated that Cd exposure contributed to the production of ROS, activated the AMPK/PPAR-γ/NF-κB pathway (increasing the expressions of P-AMPK/AMPK, NF-κB, I-κB-β, COX-2, and iNOS, decreasing the expressions of PPAR-γ and I-κB-α), finally induced autophagy (increasing the expressions of Beclin-1, the ratio of LC3-II/LC3-I and p62), and apoptosis (increasing the expressions of Bax, Bak, Caspase-9, and Caspase-3, decreasing the expression of Bcl-2). Overall, these findings revealed the vital role of AMPK/PPAR-γ/NF-κB pathway in Cd-induced liver apoptosis and autophagy, which provided deeper insights into a better understanding of Cd-induced hepatotoxicity.