Model to evaluate the toxic effect of drugs: vincristine effect in the mass of organs and in the distribution of radiopharmaceuticals in mice.
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.
Mattos
D M
DM
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. deisemar@aol.com
Gomes
M L
ML
Freitas
R S
RS
Bernardo-Filho
M
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009929:Organ Size / Q000187:drug effects*; D009928:Organ Specificity / Q000187:drug effects; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D019783:Technetium Tc 99m Dimercaptosuccinic Acid / Q000493:pharmacokinetics*; D016284:Technetium Tc 99m Pentetate / Q000493:pharmacokinetics*; D018675:Toxicity Tests / Q000379:methods; D014750:Vincristine / Q000633:toxicity*
D019275:Radiopharmaceuticals; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D014750:Vincristine; D016284:Technetium Tc 99m Pentetate