The effects of pentoxifylline on renal function and free radical production in unilateral ureteral obstruction.
There is an ongoing discussion about ureteral obstruction-related renal dysfunction. In this study, we aimed to test the effect of pentoxifylline (PTX) on both kidneys in unilateral ureteral obstruction (UUO), and to determine its interaction of with prostaglandin E2 (PGE2), and diclofenac sodium (DIS). A sham operation was performed in group 1. Placebo, PTX, DIS, and PTX+DIS were administrated to groups 2, 3, 4 and 5, respectively. The left ureter was ligated in all groups except group 1. At 24 h, technetium 99m diethylenetriamine penta-acetic acid scintigraphy was performed to determine renal function. Additionally, the tissue levels of thiobarbituric acid reactive substances (TBARS) and PGE2 in both kidneys were measured to determine cytotoxic and cytoprotective mechanisms. When the ipsilateral kidneys were evaluated: (1) UUO significantly reduced DTPA uptake and none of the medications used prevented the reduction, (2) UUO significantly increased TBARS production, and only PTX prevented the increase, (3) UUO caused a significant increase in PGE2 production, and only DIS significantly decreased this. When the contralateral kidneys were evaluated: (1) UUO significantly increased DTPA uptake but DIS and PTX+DIS prevented this, (2) UUO significantly elevated TBARS levels and DIS and PTX+DIS caused an additional elevation, (3) UUO significantly increased PGE2 production, and only DIS prevented this. In conclusion, UUO caused ipsilateral renal hypofunction and contralateral hyperfunction, which are related to increased TBARS and PGE2 levels. PTX markedly decreased free radical activity in the ipsilateral kidney. While PTX showed a placebo effect, DIS prevented the compensatory contralateral renal response through increased TBARS and decreased PGE2 levels. The beneficial effect of PTX on the ipsilateral kidney, and the hazardous effect of DIS on the contralateral kidney may be explained by more complex interactions among TBARS, PGE2, PTX, DIS and UUO-related renal dysfunction.
Department of Pediatric Surgery, Akdeniz University School of Medicine, 07070 Antalya, Turkey. adnanaslan@akdeniz.edu.tr
Adnan
A
Aslan
Güngör
G
Karagüzel
Firat
F
Güngör
Nimet
N
Izgüt-Uysal
Funda
F
Aydin
Mustafa
M
Melikoğlu
D000818:Animals; D005260:Female; D005609:Free Radicals / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000503:physiopathology*
D005609:Free Radicals; D010431:Pentoxifylline