The effect of carvedilol on serum and tissue oxidative stress parameters in partial ureteral obstruction induced rat model.
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.
Yasar A
，Erdemir F
，Parlaktas BS
，Atilgan D
，Koseoglu RD
，Saylan O
，Firat F
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《-》
Tissue malondialdehyde and adenosine triphosphatase level after experimental liver ischaemia-reperfusion damage.
Functional irregularities due to damage after ischaemia-reperfusion vary depending upon the organs affected. High energy phosphates such as ATP and ADP are destroyed after ischaemia-reperfusion damage. Subsequently, protons and inorganic phosphates accumulate within the cells and the proton pumps such as adenosine triphosphatase (ATPase), which maintain intracellular ion balance are damaged. In the present study, malondialdehyde (MDA), a product of lipid peroxidation, was measured as an indicator of tissue damage. Additionally, we measured sodium-potassium-ATPase levels and determined the interactions between MDA and Na+-K+ ATPase levels. A total of 31 female guinea pigs were divided into four groups: sham operated guinea pigs (group 1), ischaemia-reperfusion (group 2), ischaemia-reperfusion + superoxide dismutase (SOD) (group 3), ischaemia-reperfusion + allopurinol (group 4). Following reperfusion, the livers of guinea pigs in each group were removed for histopathological examination and the levels of MDA and Na+-K+ ATPase were determined in homogenized tissue samples. There was a statistically significant (p < 0.05) reduction in tissue MDA levels in group 2 when compared with group 1. The level of tissue MDA in groups 3 and 4 was significantly lower than tissue MDA levels of group 2. However, there was a statistically significant (p < 0.05) reduction in tissue Na+-K+ ATPase levels of group 2 when compared with group 1. Similarly, the level of tissue Na+-K+ ATPase in groups 3 and 4 was significantly higher than the tissue Na+-K+ ATPase levels of group 2. The results of the histopathologic examination also revealed the beneficial effects of the use of SOD and allopurinol in preventing liver damage in cases of ischaemia-reperfusion. Although the levels of MDA and Na+-K+ ATP ase in group 2 were not equal to the level in group 1, antioxidant therapy significantly improved the tendency to reverse the effects of ischaemia-reperfusion and to protect the liver from damage due to ischaemia-reperfusion.
Ilhan N
，Halifeoglu I
，Ozercan HI
，Ilhan N
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《CELL BIOCHEMISTRY AND FUNCTION》
Increased heat shock protein-70 in unilateral ureteral obstruction in rats.
Our previous studies noted the oxidative stress of unilateral ureteral obstruction (UUO). Now, we seek to explore whether UUO affects the intrinsic cellular antioxidants and triggers heat shock protein (HSP-70) and whether these are still highly expressed after reversal of the UUO (R-UUO). In addition, we designed the experiment to determine whether this expression of HSP-70 is a localized or a generalized response. Male Sprague-Dawley rats (125-150 g) were randomly assigned to sham operation, left UUO, or R-UUO procedures at six rats per group. The sham, UUO, and R-UUO animals were studied 10 days after UUO or 7 days after R-UUO. A clear increase in the left (obstructed) kidney's malondialdehyde (MDA), a marker of lipid peroxidation, was observed: a significant 2.6-fold of sham during UUO and a 1.7-fold of sham in R-UUO. The contralateral (unobstructed) right kidney showed a significant rise in MDA during UUO, but during R-UUO the MDA had fallen back to sham values. It is possibly the result of a systemic effect from the free radicals produced by the oxidative stress of the UUO. The antioxidant enzyme, manganese superoxide dismutase (MnSOD) of the left, obstructed kidney showed a significant reduction in UUO compared to that of the sham. Upon reversal of UUO (R-UUO), MnSOD was lower than that of the sham. The left kidney's HSP-70 increased during UUO and was 3.7-fold that of sham (P < 0.05) but, during R-UUO, was not different from sham (P, ns). The contralateral (intact) right kidneys' HSP-70 showed no change between sham, UUO, and R-UUO states. We conclude that UUO gives rise to oxidative stress which is generalized in both the obstructed and the contralateral unobstructed kidney, as indicated by the elevation in kidney MDA content in both kidneys. The intrinsic cellular antioxidant enzyme, manganese superoxide dismutase, showed a significant and generalized reduction in both UUO and R-UUO. In contrast, the HSP-70 was markedly elevated only in the obstructed kidney and not in the R-UUO or in the contralateral kidney, suggesting that the elevation of HSP-70 is a specific and localized response to oxidative injury of UUO.
Lin KC
，Krieg RJ Jr
，Saborio P
，Chan JC
... -
《MOLECULAR GENETICS AND METABOLISM》
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