Trace Mineral Overload Induced Hepatic Oxidative Damage and Apoptosis in Pigs with Long-Term High-Level Dietary Mineral Exposure.

The present study investigated the effects of dietary trace mineral (Cu, Fe, Mn, and Zn) supplemental strategies on liver oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis of pigs. A total of 96 Duroc × Landrace × Yorkshire (DLY) piglets were randomly divided into four groups: considered or not considered the trace mineral concentrations in basal diet, and then added to the requirements proposed by NRC (2012) (+B/NR or -B/NR); and considered or not considered the basal diet's trace mineral concentrations and then added to the level of commercial trace mineral supplement (+B/PL or -B/PL). Pigs were fed from 6.5 to 115 kg. Compared with +B/NR diets, -B/PL diets increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations (P < 0.05), resulted in high levels of Fe, Cu, Mn, and Zn accumulation in liver (P < 0.05), as well as led to hepatic oxidative damage with the high concentrations of thiobarbituric acid reactive substance (TBARS), protein carbonylation (PCO), and 8-hydroxyguanine (8-OHG) in liver (P < 0.05). Furthermore, pigs fed -B/PL diets increased CCAAT/enhancer-binding protein homologous protein (CHOP), eukaryotic initiation factor-2α (eIF-2a), interleukin-6(IL-6), B-cell lymphoma leukemia-2-associated X protein (Bax), and caspase-3, caspase-8, and caspase-9 gene expression (P < 0.05) in liver. -B/PL diets also up-regulated hepatic mRNA expression of phosphoenolpyruvate carboxykinase1 (PEPCK1), glucose-6-phosphatase (G6PC), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS) (P < 0.05) and down-regulated hormone-sensitive lipase (HSL) mRNA expression (P < 0.05) when compared with those of the + B/NR diet group. Taken together, the results indicated that long-term dietary mineral exposure with the commercial supplement level could cause harm to the structure and metabolic function of liver in pigs.