Evaluating The Toxic Effects Of Furosine By Using Mouse Model

In this study,in vitro and in vivo models were constructed to comprehensively evaluate the cytotoxicity of furosine on HePG-2,HeK-293,CaCo-2,and SK-N-SH and their toxic effects on mice.The main research contents and results are as follows:1.Effect of Furosine on In Vitro Cells: Cell viability was measured using the CCK-8 kit.The results showed that the cell viability of the furosine-treated group was significantly lower than that of the control group.Flow cytometry was used to detect cell cycle and apoptosis.The results showed that compared with the control group,furosine-treated cells in the furosine-treated group inhibited cell division in S phase,and HePG-2 and HeK-293 cells withered.Increased mortality rate 2.The toxic effects and mechanism of furosine on mice: According to the acute toxicity test of mice,the median lethal concentration(LD50)value of furosine for mice is 1.6g/kg,and the subacute toxicity is calculated based on the median lethal concentration value.The furosine concentrations in the assay were 0.1 g/kg,0.25 g/kg,and 0.50 g/kg,respectively.3.The toxic effect of furosine on mice: Results 1)Changes in body weight in mice: Body weights of mice in the furosine-treated group were significantly lower than those in the control group.2)Organ coefficient ratio: According to the mouse organ coefficient ratio,the liver index and kidney index of the male and female rats in the furosine-treated group were significantly increased.3)Routine blood test: According to the results of the hematology analyzer test,the furosine-treated group showed an increase in the total number of white blood cells(WBC),and decreased platelet(PLT)and total number of red blood cells(RBC).4)Serum biochemical indicators: The results of enzyme-linked immunosorbent assay showed that the furosine-treated group,alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(CR),and glutamyl transferase(?-GT),Malondialdehyde(MDA),total bilirubin(TBil),insulin,and uric acid(UA)content were significantly increased,while glutathione(GSH)and superoxide dismutase(SOD)contents were significantly decreased.5)Influence of tissue structure: According to the tissue section observation,the liver tissue of the high-dose furosine group(0.5g/kg)showed cell deformity,edema in some areas,and occasionally in the liver tissue of male and female rats in the high-dose group.Bleeding was observed.6)Detection of apoptotic protein in liver and kidney tissues: Western blot analysis of the protein showed that the expression of Bcl-XL and Bcl-2,the proteins that inhibit apoptosis,was significantly reduced in the furosine-treated group,and in the liver and kidney tissues.The expression of Bax and Caspase-3,the pro-apoptotic factors,increased significantly(P < 0.05)4.Effects of Furosine on Intestinal Microorganisms in Mice 16 S rRNA sequencing technology was used to detect changes in intestinal flora in mice.The results showed that the number of actinomyces and mycobacteria in the proline-treated group was significantly increased at the portal level compared with the control group(P < 0.05),and the number of prebiotics and Bacteroides in the proline-treated group was increased.Significantly increased at the genus level(P < 0.05),while the amount of Lactobacillus in the proline-treated group was significantly lower at the genus level(P < 0.05)...