The Study On Mitigation Of OTA Induced Mouse Nephrotoxicity By VE

Mycotoxins are a series of noxious secondary metabolites generated by mould, they possess extensive chemical constitution and extensive toxic effect to human being and animals. Ochratixin A (OTA) is one of mycotoxins, it is a potential threaten to the health of human being and animals because of its intense nephrotoxicity. The paper study the mechanism of mice nephrotoxicity of OTA from different aspects, includes oxidative stress reaction, pathological change, cellular damage and apoptosis in kidney. Meanwhile, the paper explores the Vitamin E (VE) from different views, as a essential nutrient for animal growth, which could relieve the mice nephrotoxicity of OTA.Experiment 1, the paper evaluates the oxidative stress reaction caused by OTA in mice renal tissue and the mitigation of VE to it, according to the detection of oxidation index and activity of antioxidant enzyme in serum and renal tissue of mice. Select healthy male mice, bodyweight range from 22 g to 25 g, intragastric administration on the study day 1, the dosage of OTA are 0, 2.5, and 5 mg/kg·BW respectively, the dosage of VE are 0, 1.5, and 15 mg/kg·BW respectively from day 1 to day 7. Sacrifice mice and collect the serum and partial renal tissue to detect the content of MDA, activity of glutathione peroxidase (GSH-Px) and Superoxide Dismutase (SOD). The results display that compare to control group, the content of MDA increases significant (P<0.05), the activity of GSH-Px decreased significant (P <0.05), the activity of SOD have decreased tendency according to the dosage increase but the difference is not significant (P >0.05) in the OTA infected group, but VE can reduce the content of MDA in mice serum and kidney in OTA infected group significantly (P <0.05), elevate the activity of GSH-Px significantly (P <0.05) in serum and tissue These results show that OTA can produce oxidative stress reaction in mice renal tissue, depress the activity of antioxidase in serum and renal tissue, thereby peroxidation intensifies in lipid of mice renal tissue. VE can improve the activity of antioxidase, relieve the reaction of lipid peroxidation on renal tissue and decrease the matter of lipid peroxidation.Experiment 2, the paper studies the pathology of mice renal tissue, in order to research the impair action of OTA to renal tissue and study the effect of VE on it. On the study day 7, collect mice urine to detect the activity of NAG, gather partial mice renal tissue into 10% formalin solution for fixation and produce pathological section. In the review of pathological section, there is no observation on the glomcrulus, no accrementition in capillary endothelial cell and intercapillary cells, no thickening of basal lamina, and no Inflammatory cell infiltration. Nevertheless, there are tubular epithelial cell apomorphosis and/or acidophilia reinforcement in renal tubule, especially in renal medulla and the conjunction of renal cortex and medulla. Meanwhile detects the activity of NAG, the activity of NAG in mice urine increases significant (P <0.05) in the OTA infected group, and the activity of NAG increases significant (P <0.05) according to increased level of OTA infected group, but in the same OTA level, the activity of NAG is depressed in the VE additional group. These results show that OTA could damage and destroy the mice renal tubular epithelial cell evidently, but VE can relieve the damage.Experiment 3, the paper uses the method of immunohistochemistry to investigate the apoptosis of kidney induced by OTA, and evaluate the action of VE for it. After processing, expose the 3'-OH terminal on DNA nucleosome fragmentation in apoptosis cell, Terminal deoxynucleotidyl transferase Mediated dUTP labeled by fluorescein isothiocyanate (FITC) to bind with the 3'-OH terminal, FITC antibody conjuncted with Peroxidase combined with FITC, use diaminobenzidine (DAB) chromogenic reagent to demonstrate the positive cell. The results display that compare to control group, the percentage of apoptosis in mice renal tubular epithelial cell increases significant (P <0.05) in OTA infected group, the percentage of apoptosis increases significant (P <0.05) according to increased level of OTA infected group. Meanwhile, adding VE can decrease the percentage of apoptosis in renal tubular epithelial cell significantly (P <0.05), the quantity of apoptosis has descent tendency according to the increased VE additional level. Observe the picture of renal tissue apoptosis it can be detected that there are typical symptom of apoptosis in the mice renal tubular epithelial cell in the OTA infected group. This also indicates that OTA can cause damage on renal tissue in cellular level, and induce the apoptosis in the mice renal tubular epithelial cell. VE have the function of relieve the renal tubular damage induced by OTA and lower the apoptosis of tubular epithelial cell in mice.All outcome of study manifest that OTA has intense toxicity to mice kidney, it can produce the oxidative stress and aggravate lipid peroxidation in renal tissue, depress the activity of antioxidant enzyme in serum and tissue. OTA can also produce the pathological changes in nephric tubule, induce Apoptosis of renal tubular epithelial cell, damage renal tissue from a series of effects. Adding VE can relieve the nephrotoxicity of OTA to a certian extent, protect the renal tissue effectively from elevating the activity of GSH-Px and decrease the degree of oxidative stress in nephridial tissue, thereby, shows the effect to minimize the toxicity caused by OTA.