As a basic trace element in the organism, iron is involved in various biological reactions, including blood oxygen transport of snow globulin, myoglobin synthesis, energy metabolism, DNA synthesis, and various enzyme reactions[1–4]. It also participates in the activation and regulation of immune system, and the proliferation and differentiation of immune cells. According to the research announced by National Research Council (NRC), sheep has the least tolerance to iron compared with other livestock.The risk of toxicosis will increase if maximum dose of iron is provided. Iron is transported to all parts of the body via blood circulation and widely distributed in sorts of tissues and organs.Therefore, excess iron will cause renal anemia, liver disease, cardiovascular disease, and nerve damage. It can also increase the susceptibility of certain viruses and bacteria[2, 9]. It has been found that impaired iron metabolism is related to many liver diseases, especially non-alcoholic fatty liver and acute or chronic liver failure. It is of vital importance to maintain iron homeostasis in cells, which is the key to cell survival. Oxidative stress and mitochondrial dysfunction are considered to be important targets of various physiological and pathological processes to the damage of excess iron to the body[11, 12]. When excess iron is exceeded, organs in the body would mainly deposit in the liver, spleen, kidney, and bone marrow Krill oil alleviates oxidative stress, iron accumulation and fibrosis in the liver and spleen of iron-overload rats[11, 13, 14]. Besides, abnormal accumulation of iron can cause damage to organs, tissue systems and metabolic disorders.
Liver is one of the key organs of the body and regulates the metabolism of carbohydrates, lipids, and proteins. It is also the center for biotransformation and detoxification of endogenous metabolites. It plays an important role in synthesis and secretion of bile salts, the absorption of bile salt-dependent nutrients, and the secretion of metabolites, innate immunity and adaptive immunity included.The liver affects the process of iron metabolism. A variety of iron-related proteins are regulated and expressed in the liver, such as hepcidin[17, 18]. It has been reported that chronic iron intake significantly increases the iron content of the liver, causing oxidative stress. Oxidative stress affected by excess iron in liver cells or Kupffer cells promotes the liver damage. A treatment strategy has been obtained for chronic liver disease by controlling iron homeostasis.
The relationship between iron and immune function has been concerned, particularly in related to the underlying inflammatory process found in diseases with chronic immune stimulation[17, 20]. The skeletal muscle produces and releases IL-6, which can increase the concentration of blood hepcidin. P. Huang has found that IL-6 and TNF-α can promote hepcidin for accelerating iron metabolic homeostasis and improve the expression of TfR224. They can be inhibited by IL-10 to down-regulate hepcidin. The expression of STAT3 can be suppressed, then improving iron metabolic homeostasis and inflammatory anemia symptoms. Iron storage can be promoted in monocytes/macrophages by increasing the expression of inflammatory factors. Hepcidin affects iron homeostasis, leading to iron excess or iron deficiency in macrophages under different conditions[7, 8].
The aim of this essay is to state the influence on the sheep liver with excess iron in the diet, affiliated by major inflammatory factors and histopathological changes. After establishing animal models with different doses of excess iron treatment, major inflammatory factors in the liver of sheep (IL-1β, IL-2, IL-6, TNF-α, IFN-γ, TGF-β1) and NF-κB content are attempted to be detected and tissue pathological changes are required to be observed, which will provide theoretical basis for studying the toxic mechanism of excess iron and the rational application of iron in sheep feeding and management.