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评估药物毒性作用的模型:长春新碱对小鼠器官质量及放射性药物分布的影响

Model to evaluate the toxic effect of drugs: vincristine effect in the mass of organs and in the distribution of radiopharmaceuticals in mice.

作者信息

Mattos D M, Gomes M L, Freitas R S, Bernardo-Filho M

机构信息

Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, RJ 20551-030, Rio de Janeiro, Brazil.

出版信息

Mutat Res. 2001 Sep 20;496(1-2):137-43. doi: 10.1016/s1383-5718(01)00224-8.

Abstract

There are evidences that the biodistribution of radiopharmaceuticals can be modified by some drugs. As chemotherapeutic drugs present important toxic effects, we studied the vincristine effect in the mass of organs and are trying to develop a model to evaluate the action of chemotherapeutic drug using the biodistribution of radiopharmaceuticals. Vincristine was administered (n=15) into female Balb/c mice, the organs isolated and their mass determined. To study the vincristine effect in the biodistribution of technetium-99m-dimercaptosuccinic acid (99mTc-DMSA) or technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA), vincristine (0.03 mg) was administered in the animals (n=15) in three doses. 99mTc-DMSA or 99mTc-DTPA was injected 1h after the last dose. After 0.5h, the animals were sacrificed and the percentage of radioactivity (%ATI) and the percentage of radioactivity per gram of tissue (%ATI/g) in each organ were calculated. The results have shown that the mass decreased significantly (Wilcoxon test, P<0.05) in thymus, spleen, ovary, uterus, kidneys, pancreas. The %ATI to 99mTc-DMSA increased in lung, pancreas, heart, thyroid, brain, and bone, and the %ATI/g increased in uterus, ovary, spleen, thymus, kidney, lung, liver, pancreas, heart, thyroid, brain and bone. To 99mTc-DTPA, the %ATI increased in uterus, ovary, spleen, thymus, kidney, lung, liver, stomach, heart and bone, and the %ATI/g increased in uterus, ovary, spleen, thymus, kidney, lung, liver, stomach, heart and bone. The results were statistically significant (Wilcoxon test). The results can be explained by the metabolization, therapeutic, toxicological or immunosupressive action of the vincristine. This model, probably, should be used to evaluate the toxic effect of various drugs.

摘要

有证据表明,某些药物可改变放射性药物的生物分布。由于化疗药物具有重要的毒副作用,我们研究了长春新碱对器官质量的影响,并试图建立一个模型,利用放射性药物的生物分布来评估化疗药物的作用。将长春新碱(n = 15)给予雌性Balb/c小鼠,分离器官并测定其质量。为了研究长春新碱对锝-99m-二巯基丁二酸(99mTc-DMSA)或锝-99m-二乙三胺五乙酸(99mTc-DTPA)生物分布的影响,以三种剂量给动物(n = 15)注射长春新碱(0.03 mg)。在最后一剂后1小时注射99mTc-DMSA或99mTc-DTPA。0.5小时后,处死动物并计算每个器官中的放射性百分比(%ATI)和每克组织的放射性百分比(%ATI/g)。结果表明,胸腺、脾脏、卵巢、子宫、肾脏、胰腺的质量显著下降(Wilcoxon检验,P<0.05)。肺、胰腺、心脏、甲状腺、脑和骨中99mTc-DMSA的%ATI增加,子宫、卵巢、脾脏、胸腺、肾脏、肺、肝脏、胰腺、心脏、甲状腺、脑和骨中%ATI/g增加。对于99mTc-DTPA,子宫、卵巢、脾脏、胸腺、肾脏、肺、肝脏、胃、心脏和骨中的%ATI增加,子宫、卵巢、脾脏、胸腺、肾脏、肺、肝脏、胃、心脏和骨中的%ATI/g增加。结果具有统计学意义(Wilcoxon检验)。这些结果可以通过长春新碱的代谢、治疗、毒理学或免疫抑制作用来解释。该模型可能应用于评估各种药物的毒性作用。

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