Effects of different combinations of dietary zinc and copper levels on the mitochondrial energy metabolism, oxidative balance, antioxidant system, and inflammation in weaned pigs

This study examined how different combinations of dietary zinc (Zn) and copper (Cu) levels affect mitochondrial ATP synthesis, redox balance, and inflammation in weaned pigs. One hundred twenty weaned pigs (7.81 ± 0.25 kg; 21 days of age) were allocated in one of four experimental treatments containing 100 (LZn) or 3000 (HZn) mg/kg of Zn as ZnO in combination with 6 (LCu) or 130 (HCu) mg/kg of Cu as CuSO4. Blood, jejunum mucosa, and liver samples were collected at weaning (d 21; pre-treatment), d 28, and d 42. High Zn diets increased hepatic mitochondrial Zn but reduced Cu concentrations at both d 28 and d 42 (P < 0.01). Basal mitochondrial oxygen consumption rate (OCR) was lower in HZnLCu compared to LZnLCu but higher for HZnHCu compared to LZnHCu at d 42 (P = 0.01). The OCR for ATP production at d 42 (P = 0.03) as well as the cytochrome c oxidase activity at d 42 (P = 0.02) and ATP concentrations at both d 28 and d 42 (P < 0.01) were lower in HZn pigs. Supplementation with HZn also reduced the activity of Cu/Zn superoxide dismutase (Cu/Zn-SOD) at both d 28 and d 42 and total glutathione peroxidase (GPx) at d 42 (P < 0.01). However, HCu increased cytosolic Cu/Zn-SOD activity (P = 0.03) and both total and mitochondrial GPx activities at d 28 (P = 0.01). In the jejunum mucosa, HZn increased cytosolic/mitochondrial superoxide dismutase (SOD) activity at d 42 (respectively, P = 0.08 and P < 0.01), but reduced total GPx activity at d 28 (P = 0.07). In contrast, HCu increased total GPx activity at d 28 (P = 0.09). In plasma, IL-1β and TNF-α concentrations were higher for HZn pigs at d 28 (P ≤ 0.03), while protein carbonyl concentrations and SOD activity were not affected by treatments at both d 28 and d 42 (P ≥ 0.20). However, HZn reduced tight junctions related genes expression at d 42 (P ≤ 0.05). The GPx activity in plasma was lower for HZnLCu compared to LZnLCu but higher for HZnHCu compared to LZnHCu pigs at d 28 (P = 0.04); by d 42, GPx activity was lower in HCu groups (P = 0.01). In conclusion, high Zn diets in pigs led to hepatic Zn accumulation and Cu depletion, impairing liver mitochondrial function. Whereas high Zn diets apparently compromised the jejunum mucosal integrity, the effects on the antioxidant response were tissue-specific.