Verapamil attenuates renal tubular apoptosis in response to partial unilateral ureteral obstruction.
BACKGROUND
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.


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).


CONCLUSIONS
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.
Topcu
Sukru Oguzkan
SO
Department of Urology, Sahinbey Hospital, University of Gaziantep Medical School, Kolejtepe/Gaziantep, Turkey. oguztopcu@hotmail.com
Erbagci
Ahmet
A
Erturhan
Sakip
S
Yagci
Faruk
F
Ucak
Ramazan
R
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D007150:Immunohistochemistry / Q000379:methods; D007684:Kidney Tubules / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D011817:Rabbits; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D014513:Ureter / Q000473:pathology; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000473:pathology*; D014665:Vasodilator Agents / Q000627:therapeutic use*; D014700:Verapamil / Q000627:therapeutic use*; D019014:fas Receptor / Q000096:biosynthesis
D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D014665:Vasodilator Agents; D019014:fas Receptor; D014700:Verapamil