Histological changes, lipid metabolism, and oxidative and endoplasmic reticulum stress in the liver of laying hens exposed to cadmium concentrations

Abstract

The objective of this study was to determine the effects of cadmium (Cd) on histological changes, lipid metabolism, and oxidative and endoplasmic reticulum (ER) stress in the liver of layers. A total of 480 hens at 38 wk of age were randomly assigned in 5 groups that were fed a basal diet or basal diet supplemented with CdCl₂ 2.5H₂O at 7.5, 15, 30, and 60 mg Cd/kg feed for 9 wk. The results showed that accumulation of Cd was the greatest in the kidney, followed by the liver, pancreas, and lung. Diet contaminated with 30 mg Cd/kg induced antioxidant defenses accompanied by the increase of the activities of antioxidant enzymes in the liver, while dietary supplementation with 60 mg Cd/kg decreased the antioxidant levels significantly (P < 0.05). Immunofluorescence assay showed Cd induced reactive oxygen species production and endoplasmic reticulum stress in hepatocytes. Exposure to 60 mg Cd/kg significantly upregulated the expression of cytochrome C, caspase 3, caspase 9, caspase 7, Grp78, and Chop (P < 0.05). Histopathology and quantitative real-time PCR results presented periportal fibrosis, bile duct hyperplasia, and periportal inflammatory cell infiltration in the liver accompanied by upregulating the expression of tumor necrosis factor-α, IL-6 and IL-10 in the 30- or 60-mg Cd/kg groups. Oil Red O staining and RT-qPCR results showed dietary supplementation with 7.5, 15, and 30 mg Cd/kg promoted the synthesis of lipid droplets and upregulated the expression of fatty acid synthase, while dietary supplementation with 60 mg Cd/kg attenuated the synthesis of lipid droplets and downregulated the expression of acyl-CoA oxidase 1, carnitine palmitoyltransferase-1, and perixisome proliferation-activated receptor α (P < 0.05). Besides, the expression of vitellogenin (VTG) II and microsomal triglyceride transfer protein were upregulated in the 7.5-mg Cd/kg group, and the expressions of apolipoprotein B, vitellogenin II, and apolipoprotein very-low-density lipoprotein-II were downregulated in the 30- and/or 60-mg Cd/kg groups (P < 0.05). Conclusively, although low-dose Cd exposure promoted the synthesis of lipids and lipoproteins in the liver, the increase of Cd exposure could trigger liver injury through inducing oxidative and endoplasmic reticulum stress and negatively affect lipid metabolism and yolk formation in laying hens.

Keywords: cadmium; endoplasmic reticulum stress; laying hens; lipid metabolism; liver.