Action of tacrolimus on Wistar rat kidneys implanted with Walker 256 carcinosarcoma

Abstract

Purpose:To evaluate the development of Walker 256 tumor in male Wistar rats treated with tacrolimus using an experimental kidney tumor model. Methods: 40 male Wistar rats were divided into four groups: Tumor group (TU) (n=10), Tacrolimus-Tumor group (TT) (n=10), Tacrolimus group (TC) (n=10) and Control group (C) (n=10). Treatment with tacrolimus was performed in groups TT and TC. Under anesthesia, the right kidney of each animal of TU and TT was accessed through a supraumbilical incision and inoculated with a 0.1mL solution containing 2x10 6 tumor cells (Walker 256 carcinosarcoma tumor cells). Group TC was treated with a saline solution. All the animals of groups TC and TT were treated with tacrolimus (5mg/kg/day) by gavage for 15 days. TU group animals received saline by gavage for 15 days. On the 15th postoperative day, all animals were submitted to euthanasia and blood sampling for analysis of serum creatinine (Cr) and blood urea nitrogen (BUN). Abdominal gross examination was performed, the right kidney removed and prepared for histological analysis by hematoxylin-eosin staining. The resulting data were submitted to statistical analysis by ANOVA. Results: Statistical significance was found when comparing creatinine level between groups TU, TT and TC -TT group culminated with a marked increased in creatinine levels (Cr=1.013 ± 0.3028 mg/mL), TU group (Cr=0.5670 ± 0.03536 mg/dL) P=0.00256, TC group (Cr =0.711 ± 0.1653 mg/mL) P= 0.02832. Statistical significance was found when comparing BUN levels in TT group (71.32 ± 17.14 mg/mL), compared with TU group (45.83 ± 5.046 mg/dL), P=0.000318. There were no statistically significant differences between groups TT and TC (61.23 ± 9.503 mg/mL) P=0.7242. Histological analysis showed a poor evolution in TT group with multiple foci of hemorrhage and cortical invasion by the Walker tumor. Conclusion: The Tacrolimus-treated group developed a more aggressive tumor and a drug-related nephrotoxic effect. Key words: Carcinoma 256, Walker. Tacrolimus. Tacrolimus Binding Proteins. Rats. RESUMOObjetivo: Avaliar as alterações na evolução do carcinosarcoma 256 de Walker, inoculado no rim de ratos Wistar, sob tratamento imunossupressor com o tacrolimus. Métodos: Foram utilizados 40 ratos Wistar, machos divididos em quatro grupos de 10: grupo Tumor (TU), Tumor-Tacrolimus (TT), Tacrolimus (TC) e Controle (C). Os ratos dos grupos TU e TT foram inoculados com 0,1 mL de solução contendo 2x10 6 células do tumor de Walker no parênquima do rim direito. Os dos grupos TC e TT receberam tratamento com tacrolimus na dose de 5mg/kg de peso, via gavagem orogástrica durante 15 dias. Os ratos do grupo TU receberam solução salina isotônica pH 7,2. Ao 15º dia de evolução, todos foram submetidos à eutanásia. Amostras de sangue eram coletadas para dosagem de creatinina (Cr) e uréia (Ur) e posteriormente realizada nefrectomia para avaliação histológica. Resultados: As dosagens séricas de creatinina foram maiores no grupo TT (Cr = 1,013±0,3028 mg/mL), que diferiu significantemente dos grupos TU (...

Analysis of the histology of the scar bladder and biochemical parameters of rats with a solitary kidney undergoing immunosuppression with tacrolimus

“…The biochemical and histological effects of tacrolimus has been demonstrated in various organs in various animal studies4,5,9 . The evaluation of creatinine and urea in Wistar ratshas well established parameters under normal conditions.…”