Action of tacrolimus on Wistar rat kidneys implanted with Walker 256 carcinosarcoma.
OBJECTIVE
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 0.1 mL solution containing 2 x 10(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 + or - 0.3028 mg/mL), TU group (Cr=0.5670 + or - 0.03536 mg/dL) P=0.00256, TC group (Cr =0.711 + or - 0.1653 mg/mL) P= 0.02832. Statistical significance was found when comparing BUN levels in TT group (71.32 + or - 17.14 mg/mL), compared with TU group (45.83 + or - 5.046 mg/dL), P=0.000318. There were no statistically significant differences between groups TT and TC (61.23 + or - 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.


CONCLUSIONS
The Tacrolimus-treated group developed a more aggressive tumor and a drug-related nephrotoxic effect.
Inácio
Cristiano Machado
CM
Evangelic Faculty of Parana, University Evangelic Hospital, Curitiba, PR, Brazil. ipem@evangelico.org.br
Dietz
Ulrich Andréas
UA
Malafaia
Osvaldo
O
Ribas Filho
Jurandir Marcondes
JM
Nassif
Paulo Afonso Nunes
PA
Czeczko
Nicolau Gregori
NG
Marcondes
Carmen Australia Paredes
CA
D000704:Analysis of Variance; D000818:Animals; D001806:Blood Urea Nitrogen; D002279:Carcinoma 256, Walker / Q000473:pathology*; D003401:Creatine / Q000097:blood; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007680:Kidney Neoplasms / Q000473:pathology*; D016030:Kidney Transplantation; D008297:Male; D009368:Neoplasm Transplantation; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D003401:Creatine; D016559:Tacrolimus