The effect of carvedilol on serum and tissue oxidative stress parameters in partial ureteral obstruction induced rat model

Abstract

Although the pathological mechanism underlying kidney damage is not completely understood, it has been reported that reactive oxygen species (ROS) formed during ureteral obstruction may play an important role in this process. Carvedilol has been used in a limited number of studies examining oxidative injury. The aim of this study was to investigate the effect of carvedilol on serum and tissue oxidative stress parameters in the partial unilateral ureteral obstruction (PUUO)-induced rat model. To our knowledge, the protective effects of carvedilol in the PUUO-induced rat model have not been reported. Twenty-six male Wistar albino rats, age 5.5 to 6 months and weighing 250 to 300 g, were used in this study. The rats were randomly divided into three groups. In Group 1 (n = 9), the control group, a sham operation was performed. In Group 2 (n = 8), the PUUO group, the left ureter was embedded into the psoas muscle to create PUUO and maintained for 7 days. In Group 3 (n = 9), carvedilol was orally administered to the rats (2 mg/kg). After the establishment of PUUO, carvedilol was given for the following 7 days. After partial unilateral ureteral obstruction, a nephrectomy was performed to determine the blood and tissue levels of superoxide dismutase (SOD), malondialdehyde (MDA), protein carbonyl (PC), and nitric oxide (NO). The median SOD, MDA, PC, and NO levels in the tissues were 0.006 U/mg protein, 5.11 nmol/g protein, 4.31 nmol/mg protein, and 0.337 μmol/g protein in the control group, respectively. There was a significant increase in tissue SOD (p = 0.014), MDA (p = 0.002), and NO (p = 0.004) levels in Group 2. However, a statistically significant difference was not observed in PC (p = 0.847) enzymatic activity in Group 2. When compared with Group 2, carvedilol treatment caused a reduction in NO (p = 0.003), and PC (p = 0.001) activities in Group 3. The serum SOD (p = 0.004), MDA (p = 0.043), PC (p = 0.043), and NO (p = 0.001) levels were significantly different in Group 3 compared with Group 2. Administration of carvedilol also reduced the detrimental histopathologic effects caused by PUUO. According to histopathological examination of the renal tissues, the inflammation rates were 22.2%, 87.5% and 33.3% in Groups 1, 2, and 3, respectively (p < 0.05). The results of the present study show that partial unilateral ureteral obstruction caused oxidative stress in the serum and kidney tissues of rats, and treatment with carvedilol reduced the harmful effects of ureteral obstruction.

Attenuation of partial unilateral ureteral obstruction-induced renal damage with hyperbaric oxygen therapy in a rat model

“…As renal blood flow increases in the first 12 hour period after obstruction, hypoperfusion develops in advancing periods and is called secondary vascular injury. In current publications it is reported that ROS may lead to severe injury to the cell membrane by lipid peroxidation reactions and may have an important role in tubulointerstitial inflammation associated with obstructive nephropathy (3,4,14). Additionally, apoptosis has been reported to play an important role in pathophysiology of obstructive renal parenchymal injury (4).…”

“…Upper urinary tract obstruction is most often secondary to calculi, strictures, tumors and ureteropelvic junction or ureterovesical junction obstruction and is usually a reversible and partial unilateral condition (4). Although ureteral obstructions may cause kidney parenchymal damage due to several mechanisms, the exact pathophysiological mechanism of the changes in UPUO has not been fully understood (3,14). Intrarenal collecting system pressure elevation, renal blood flow impairment, vasoactive and inflammatory mediators are some of the known factors in pathophysiology of renal damage arising from UPUO (3, 4).…”

“…Taking into account previous studies, the sections were evaluated and scored for tubular dilatation (TD), interstitial inflammatory cell infiltration (IICI), intertubular hemorrhage and congestion (IHC), interstitial fibrosis (IF), and tubular cast (TC) (13). Tissue damage scores were no visible change [0], minimal or slight change [1], moderate change [2], and severe change [3]. After calculating the score for each of the histopathological changes, the total score was obtained by addition of all the scores from tissue damage markers.…”

“…In clinical practice, although unilateral partial ureteral obstruction (UPUO) is considerably more common, the pathophysiologic changes in renal tissue due to UPUO are not understood as well as those in complete ureteral obstruction (2). Known factors in the pathophysiology of the partially obstructed kidney are characterized by renal blood flow impairment, intrapelvic pressure elevation, vasoactive and inflammatory mediators (3). Reactive oxygen species (ROS), which form during ureteral obstruction, are recently recognized as responsible for the development of the pathogenesis of UPUO in experimental research (2,3).…”

“…Known factors in the pathophysiology of the partially obstructed kidney are characterized by renal blood flow impairment, intrapelvic pressure elevation, vasoactive and inflammatory mediators (3). Reactive oxygen species (ROS), which form during ureteral obstruction, are recently recognized as responsible for the development of the pathogenesis of UPUO in experimental research (2,3). Increased lipid peroxidation and oxidative stress in UPUO have been proposed as possible causes that lead to tubule-interstitial lesions and renal fibrosis.…”