人工合成铁(Ⅱ)酪氨酸SOD模拟物的毒性及血清半衰期研究

A Preliminary Study of Toxicity and Efficacy of SOD Simulacrum: Fe^(++) -Tyrosine Compound

通过灌胃急性毒性、慢性毒性、遗传毒性和灌胃后吸收入血清的药时变化对人工合成的铁(Ⅱ)酪氨酸SOD模拟物的毒性及其吸收后血清半衰期进行了初步探索,研究结果表明:此物对小鼠灌胃的LD50为大于5 000 mg/kg。以不同剂量连续给药一月后,小鼠的心、肝、胸腺、脾、肺、肾和肠胃等脏器在形状、大小和颜色上与正常组无明显差异;用不同剂量给小鼠灌胃,小鼠的嗜多染红细胞微核率为2.67±0.65‰,1.92±0.89‰和1.83±0.71‰,仅高剂量组有一定增长(P<0.05);经不同浓度给药后,血清中血药浓度峰值时间为60～270 min,半衰期为160～360 min。证明此药为微毒物质,适当剂量口服后无明显蓄积毒性,大剂量使用时可导致一定的染色体损伤,血清药浓度半衰期随给药浓度有所变化。可望在植物生长调节剂、医药或化妆品、饲料、食品中的抗氧化添加剂及着色抑菌的防腐添加剂等中代替天然SOD。

For the purpose of examining the toxicity and efficacy of Fe＋＋-Tyrosine and providing reference for its applications,acute toxicity,chronic toxicity and polychromatic erythrocyte（PCE） micronucleus rate（MNR） tests in mice were conducted.In addition,SOD activity changes in mice blood were measured after oral exposure.Results turned out that the half dose（LD50） was found to be more than 5000mg /kg by oral administration,which fell in the category of light toxicity according to the acute toxicity classification（WHO,1997）.After one month’ s continuous affusion with different dosages and anatomization,there were no obvious differences between the group of Fe ＋ ＋-Tyrosine affusion and the negative control group in the index of color,shape and size in levers,spleens,kidneys,lungs and thymus.Consecutive stomach dosing showed no obvious influence on the mice organs,which means that under the experimental conditions Fe ＋ ＋-Tyrosine has no cumulative toxicity.After affusion with the dosages,the PCE micronucleus rates（‰） were 2.67 ± 0.65,1.92 ± 0.89 and 1.83 ± 0.71 respectively.High dosage could increase the micronucleus rate（P 0.05）.After the stomach dosing at dosage of 800mg / kg,400mg /kg,200mg /kg,the medicine peak times in mice blood appeared at 60 to 210 minutes and the serum half-life times were about 160 to 360 minutes individually.It is expected that it can replace natural SOD inplant growth regulator,medicine,cosmetics,feed,food antioxidant and food coloring and anti-bacteria additives.