Login to Access Video or Poster Abstract: MP100-08
Sources of Funding: Thompson Family Foundation

Introduction

WST11-VTP is a promising technology in cancer treatment. Several preclinical models demonstrated higher efficacy in ablation of prostate, urothelial and kidney tumors. Likewise others ablation procedures, some normal tissue beyond the tumor’s area can be affected causing some undesirable effects. Sveto et al showed the capacity of SS-20 and SS-31 peptides in reduce cells damage after ischemic kidney injury in rats. We examined combination of VTP and SS peptides on kidney tissue damage after high-dose VTP application

Methods

28 black-6 male mice arranged in 4 different groups: VTP alone, VTP plus SS-20, VTP plus SS-31 and VTP plus SS-20 and SS-31. All mice got same high dose of VTP – 200 mW/cm / 10’ – and retro-orbital WST11. The SS peptides dose was 2mg/Kg, gave 30’ before VTP and daily for 4 days by subcutaneous injection. In the VTP plus SS-20/ SS-31 combination group, a single shot of SS-20 was used 30’ before VTP and the following daily doses were just SS-31. All VTP application was performed on left kidney after surgical approach by small flank incision and renal externalization. Urea and creatinine blood exam were realized one day before VTP, 24 hrs and 72 hrs after. All mice were euthanized on day 5 after VTP and tissues of interest were collected for histology assessment by a board certificated pathologist

Results

After 28 mice submitted a VTP high dose treatment, just one from VTP alone group died. A reduced kidney damage- analyzed by tubular injury score- was observed in all peptides groups compare to VTP alone, but only the SS-20/SS-31 combination showed a statistical significance ( p < 0.05) . As a single agent, SS-20 seems has a better effect in kidney protection compares to SS-31. The E-Cadherin grades were lowered in all peptides treatment groups compared to VTP only (positive effect), but do not reach significance. This may be mitigated by powering the study to include more animals in each cohort. The same fact was observed in creatinine and urea results analysis. Compare to VTP alone, all peptides groups had lower creatinine and urea values 24 hrs after VTP application, but without statistical importance. Exception for SS-31 and VTP alone groups that reached statistical difference (p=0.04) in the urea measures 24 hrs after VTP. Once again, SS-20/SS31 combination and SS-31 groups presented lowest levels of creatinine and urea on day after VTP. After 72 hrs of VTP application, creatinine and urea returned to baseline values in all groups

Conclusions

The use of mitochondria-target peptides, SS-20 and SS-31, can protect the kidney against high dose VTP in a mouse model. The rationale of combine this drugs before and after VTP seems a promising approach in renal preservation and side effects prevention after VTP ablation

Funding

Thompson Family Foundation