Effects of Apo-ester granules on liver and kidney tissue toxicity， serum inflammatory factors and humoral immunity in mice

【Objective】The effects of long-term addition of Apo-ester（APO）granules on the structure and function of liver，kidney and humoral immunity levels in Kunming mice were investigated，and its safety was systematically evalua-ted，which would provide a reference for the scientific application of APO in livestock and poultry production.【Method】 The median lethal dose（LD₅₀）of APO granules was measured by acute toxicity test on Kunming mice. Then，50% LD₅₀ （1.4 g/kg）and 80% LD₅₀（2.2 g/kg）were set as dose groups and equal amount of saline was used as blank control. After a single gavage of 1.4 g/kg APO suspension，eye blood was collected on the 4^th，12^th，36^th and 60^th h and on the 7^th d and 14^th d after the gavage for the determination of blood routine indexes. After 21 d of continuous gavage of APO suspension at 1.4 and 2.2 g/kg，the weight gain，blood biochemical indexes，urinary indexes immune indexes of mice were analyzed. Besides，the liver and kidney were collected for histological observation in paraffin sections.【Result】The LD₅₀ of APO granules on Kunming mice was 2.74 g/kg with the 95% confidence limit of 2.69-3.41 g/kg. According to the toxicity grading standard of WHO，APO granule was a low-toxicity substance. The blood neutrophils of Kunming mice increased significantly（P<0.05，the same below）at the 4^th h after single gavage of APO suspension at a dose of 1.4 g/kg. The total number of white blood cells was significantly increased at 12^th and 36^th h after gavage，and the number of lymphocytes was extremely significantly increased at 4^th and 12^th h after gavage（P<0.01，the same below）. The total number of erythrocytes and the mean erythrocyte hemoglobin content increased significantly at 36^th h after gavage. The body weight gain and mean daily weight gain of Kunming mice were extremely significantly reduced after 21 d of continuous gavage of APO suspension at a dose of 2.2 g/kg. Serum alkaline phosphatase activity and urea content were extremely significantly increased，while tangrass transferase activity and creatinine content were extremely significantly reduced. The number of white blood cells，the levels of urinary microalbumin and ketone body in the urine were increased significantly. Liver yellowing，congestion，disorder of hepatic cord and sinusoids，the fragmentation and dissolution of liver cells even swelling or necrosis were observed. The kidneys were obviously enlarged and yellowish. The renal corpuscle was broken and extinct，and medulla showed diffuse hemorrhage. Serum levels of immune cytokines IL-1β，TNF-α and IL-10 were significantly or extremely significantly increased，while the concentrations of immunoglobulins IgM and SIgA were significantly decreased.【Conclusion】APO granules are low-toxic substances，while high-dose addition can lead to the rapid increase of blood cells，and the tissue structure of liver and kidney in mice can also be damaged. Furthermore，the humoral immunity can be inhibited. Therefore，it is recommended not to add excessive amounts or long-term addition in poultry production. The mixing ingredients should be ensured uniformity to avoid the damage of liver and kidney function through ingesting high doses of APO.