Verapamil Attenuates Renal Tubular Apoptosis in Response to Partial Unilateral Ureteral Obstruction

Abstract

Introduction: Partial unilateral ureteral obstruction (PUUO) is the type of obstruction that is most often encountered in pediatric clinical practice. The majority of our knowledge on PUUO has been derived from experimental studies and the effects of PUUO on the kidney have still been a source of continual investigation. Material and Methods: In the present study, renal expression of p53, Fas and PCNA were examined in rabbits with long-term (4 weeks) partial obstruction. Additionally, the effect of calcium channel blocker on pronounced apoptotic changes were evaluated. Results: Immunohistochemistry results revealed that PUUO for 4 weeks caused an upregulation of p53 to 55.2 ± 2% and Fas to 30.1 ± 1.1%, whereas verapamil challenge attenuated the expression of these two apoptotic markers (p53: 15.9 ± 1.8%; Fas: 18.2 ± 1.4%, p < 0.05). Importantly, PCNA activity was also increased in response to PUUO. However, verapamil treatment after onset of obstruction caused a markedly decrease in the expression of PCNA (42.9 ± 10.8% vs. 9.6 ± 2.1%, PUUO, PUUO + verapamil; respectively, p < 0.05). Conclusion: The expression of p53, Fas and PCNA molecules is associated with long-term partial ureteral obstruction, whereas verapamil seems to be a protective agent against apoptotic changes.