Tehran University Medical Journal

---

Background: Ureteral obstruction, leading to urinary stasis and elevated pressure in the proximal part of urinary tract, causes progressive renal dysfunction. This study was designed to evaluate the status of oxidative stress and metabolic defect in acute unilateral ureteral obstruction (UUO).

Methods: Experiments were performed on three groups of male Sprague-Dawley rats (n=10 in each group). In the UUO group, rats were lightly anesthetized by ether and the left ureter was occluded by means of a sterile surgical procedure. Twenty-four hours after UUO-induction, both kidneys were removed and stored at -70 °C. In the sham group, anesthesia and surgery were performed without ureteral occlusion, and the control group received no surgical procedure. The kidney samples were assessed to measure the levels of ATP and ADP by the luciferin-luciferase method for determining metabolic status. In addition, the levels of malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP) of the kidneys were measured to evaluate the redox state. Data are expressed as means ±SEM per gram of kidney weight (gKW). The comparisons were performed using paired t-test for intra-group analysis, and ANOVA followed by Duncan's post-hoc test and then LSD test for inter-group analysis. Significance was taken at p<0.05.

Results: The comparisons between the UUO and sham groups indicated that 24 hours of UUO increased levels of MDA (51.42±1.86 vs. 38.64±1.02 nmol/gKW, respectively p<0.001) and ADP (0.67±0.04 vs. 0.47±0.045 µmol/gKW, respectively p<0.01), but decreased levels of FRAP (2.44±0.18 vs. 4.28±0.27 µmol/gKW, respectively), ATP (1.09±0.10 vs. 2.26±0.19 µmol/gKW, respectively) and ATP/ADP ratio (1.64±0.14 vs. 5.11±0.56, respectively) in the obstructed kidneys, all p<0.001. In the non-obstructed kidneys, the levels of ATP and ADP were higher (p<0.01 and p<0.001, respectively), while the levels of MDA and ATP/ADP ratio were equal to those of the sham group.

Conclusion: Twenty-four hours of acute UUO induces oxidative stress and reduces the aerobic metabolism in obstructed kidneys, whereas non-obstructed kidneys with a normal redox state show the higher levels of metabolism.

---

Background: Obstructive nephropathy has been associated with disorders in metabolism state and oxidative balance of kidney. Stress oxidative play a key role in the pathophysiological processes of renal diseases. The objective of this study was to investigate effects of vitamin-E, as a powerful antioxidant, on renal oxidative stress and metabolism defect induced by 24-hr unilateral ureteral obstruction (UUO).

Methods: Anesthetized male Sprague-Dawley rats (n=10 in each group) were sterilely operated to occlude the left ureter. In UUO+NS, we had a single dose normal saline injection and in UUO+VitE and UUO+OO groups, D-α-tocopherol (50 mg/kg), the main component of vitamin-E, and its vehicle (Olive Oil), respectively, were twicely infused I.P. before and after UUO-induction. There were also sham-operated and control groups. 24-hr after of UUO-induction, both kidneys were removed and stored in -70°C. To determine metabolism condition, the levels of ATP and ADP and to evaluate redox state, the levels of malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP) of kidneys were assessed.

Results: The comparisons between UUO+NS and sham groups indicated that UUO increased MDA (p<0.001) and ADP (p<0.05), but decreased FRAP, and ATP/ADP ratio in obstructed kidney (all p<0.001). In UUO+VitE group, MDA and FRAP were equal to their levels in sham group, while ATP, ADP and ATP/ADP ratio were not different from those of UUO+NS group in obstructed kidney.

Conclusion: Twenty four hour of UUO caused renal reduction in oxidative metabolism and elevations in reactive oxygen species and administration of vitamin-E, although considerably ameliorated the oxidative stress, could not improve the defected metabolism.

---

Background: Ureteral obstruction has been shown to induce renal oxidative stress, suppressed energy metabolism and defected acid excretion. This study was aimed to examine the improving effects of L-carnitine, a facilitating cofactor for mitochondrial oxidation of fatty-acids as well as a scavenger of free-radicals, and -tocopherol as the most potent antioxidant on these renal disorders at early hours following release of unilateral ureteral obstruction.
Methods: The left ureter was ligated in 60 anaesthetised rats, L-carnitine, -tocopherol, or their vehicles (normal saline and olive oil, respectively) were injected (i.p.) in four groups. Each rat was re-anesthetized and cannulated, and ureteral legation was released at exactly 24h after UUO-induction. A 30-min clearance period performed to separately collect urine from both kidneys. The collected urine and arterial blood samples were given to pH-gas analyzer and autoanalyzer, and malondialdehyde (MDA), ATP and ADP levels were assessed in preserved kidneys. There were also sham and control groups (n=8-10 in each).
Results: In the post-obstructed kidney of vehicle-treated groups with respect to the equivalent kidney of sham group, there were increases in MDA (p<0.001), ADP (p<0.01), urinary pH (p<0.001), absolute (p<0.05) and fractional bicarbonate excretions (p<0.01), but decreases in ATP, ATP/ADP (both p<0.001), and urinary PCO2 (p<0.01). -tocopherol could normalize MDA level but did not affect the altered amounts of energy metabolic indices and acid-base excretions, while L-carnitine improved all of them except of decreased urinary PCO2.
Conclusions: Increased bicarbonate-excretion in post-obstructed kidney is due to defected acid-secretion at collecting duct, which is not related to ureteral obstruction-induced renal oxidative stress and suppressed energy metabolism.