5-羟甲基糠醛的急性毒性和细胞毒性研究

Study on Acute Toxicity and Cytotoxicity of 5-Hydroxymethylfurfural

目的考察5-羟甲基糠醛(5-HMF)对ICR小鼠的急性毒性及其对肥大细胞模型RBL-2H3和P815细胞的毒性。方法用8种不同剂量的5-HMF溶液对ICR小鼠进行尾静脉给药,每日观察小鼠行为情况,测定小鼠体重,记录死亡数,并计算半数致死量(LD50),观察期结束进行病理学检查;采用MTT法测定5-HMF溶液对RBL-2H3细胞和P815细胞的毒性影响,并计算IC_(50)。结果小鼠尾静脉给药后低剂量出现共济失调、强直性抽搐等现象,随着剂量升高,出现以上现象频率升高;在体重方面,最高剂量雄性给药后d1到恢复期结束d14,与对照组相比体重显著降低(P<0.01),雌鼠给药后d1~d14,体重比对照组显著降低(P<0.01),次高剂量雌鼠给药后d1、d11、d14体重有所减低(P<0.05),d4~d7显著降低(P<0.01);存活动物组织病理学检查结果提示5-HMF组诊断为慢性进行性肾病,利用Bliss法计算小鼠ICR急性毒性LD50为871.12 mg·kg^(-1);利用MTT法测定5-HMF对于肥大细胞RBL-2H3和P815的IC50分别为4.96 mM和7.43 mM。结论 5-HMF具有一定的急性毒性,LD50为871.12 mg·kg^(-1),毒性靶器官为肾脏。对两种细胞的IC_(50)分别为4.96 mM和7.43 mM,上述结果为该物质的安全应用及其对肥大细胞的脱颗粒作用深入研究提供了参考数据。

Objective To investigate the acute toxicity of 5-hydroxymethylfurfural（5-HMF） on ICR mice and cytotoxicity on mast cell RBL-2 H3 and P815. Methods ICR mice received tail vein injection of 8 different doses of 5-HMF.The mice were observed daily to record the number of death and body weight, then 50 % lethal dose of（LD_（50）） wascounted. Pathological examination was completed at the end of the observation period. The cytotoxicity of 5-HMF on mast cell： RBL-2 H3 and P815 was measured by MTT assay and 50 % inhibitory concentration（IC_（50）） was calculated.Results Ataxia, tonic convulsions and other phenomena appeared in low doses, and with the dose increasing the frequency of above phenomenon increased. 5-HMF significantly decreased the weight of all groups from d1~d14 compared with control group（P 0.01） and the LD_（50） value was 871.12 mg·kg^（-1） using Bliss method based on the mortality rate. Pathological examination showed that mice had chronic progressive nephropathy in all doses. The IC_（50） of 5-HMF solution on RBL-2 H3 and P815 was respectively 4.96 mM and 7.43 mM. Conclusion 5-HMF has acute toxicity with LD_（50） 871.12 mg·kg^（-1）, and kidney is the toxic target organ. IC_（50） in RBL-2 H3 and P815 is4.96 mM and 7.43 mM respectively. It provided the experimental basis for the degranulation of mast cells and theoretical basis for its quality control and further safety research.