Excess Iron added to the diet induces the apoptosis of chicken’s liver through the PI3KAKT mTOR axis

Abstract

Iron (Fe), an essential trace element, plays a key role in biological metabolism. The PI3K/AKT/mTOR axis plays an important role in the control of apoptosis. However, the effect of iron overdose in the diet on the role of the PI3K/AKT/mTOR axis and apoptosis, and pathological liver damage in chickens are still poorly understood. In this study, 180 1-day-old chicks were divided into 3 groups, which were fed the basal diets supplemented with 50 (C), 500 (E1), and 1000 (E2) mg Fe/Kg as ferrous sulfate monohydrate (FeSO4·H2O) and returned to normal diet one day later, Tested on days 1, 3, 7, 14, and 21 after the end of the iron addition. The results showed that the liver morphology was normal in the group C. The groups E1 and E2 showed the structure destroyed of hepatic lobules, the disordered of hepatic cords, the reduction of the central veins and the presence of erythrocytes accompanied by inflammatory cell infiltration. The group E2 showed more serious damage than the group E1, but these phenomena will largely return to normal on day 21. The perls staining showed that large deposits of iron-containing hemosiderin in the hepatic sinus after iron overdose intake, and the changes of iron deposition and pathological damage had certain regularity in time. The expression of Bax, Caspase-3, Caspase-8, and Caspase-9 in groups E1 and E2 were increased from days 1 to 21, which was in contrast to the Bcl-2, and it has a dose dependent. This suggested that iron overdose triggered apoptosis, which was supported by our ultrastructural observations of chromatin marginalization and impaired mitochondrial swelling. In addition, the expression of PI3K and AKT were significantly increased in the iron overdose groups, while the expression of mTOR was decreased. Above all, iron overdose can induce apoptosis in chicken hepatocytes through regulation of the PI3K/AKT/mTOR axis, leading to pathological damage. The type of iron overdose-induced damage was dose-dependent but not permanent. These results provide a theoretical basis for a comprehensive understanding of the importance of mineral nutrition management in poultry and the possible risk of excessive iron intake.