Melatonin Attenuates Unilateral Ureteral Obstruction–Induced Renal Injury by Reducing Oxidative Stress, iNOS, MAPK, and NF-kB Expression

Özbek, Emin; İlbey, Yusuf Özlem; Özbek, Mustafa; Şimşek, Abdülmuttalip; Çekmen, Mustafa; Somay, Adnan

doi:10.1089/end.2009.0035

Cited by 75 publications

(67 citation statements)

References 51 publications

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“…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).…”

Section: Discussionmentioning

confidence: 99%

“…Increased lipid peroxidation and oxidative stress in UPUO have been proposed as possible causes that lead to tubule-interstitial lesions and renal fibrosis. Furthermore, apoptotic cell death has been reported to play an important role in renal damage arising from UPUO (4). Despite advances in supportive precautions and preventive strategies, presently there is no specific medication in clinical use for UPUO-induced renal damage.…”

Section: Introductionmentioning

confidence: 99%

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

Sancak¹,

Tan²,

Türkön³

et al. 2017

European Urology Supplements

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ARTICLE INFO ______________________________________________________________ ______________________Objective: The objective of the present study was to evaluate the effectiveness of HBO therapy on biochemical parameters, renal morphology and renal scintigraphy in rats undergoing chronic unilateral partial ureteral obstruction (UPUO). Material and methods: Thirty-five rats were divided into five equal groups: Control group; Sham group; HBO group; UPUO group and UPUO/HBO group. The effects of HBO therapy were examined using biochemical parameters and histopathological changes. After calculating the score for each histopathological change, the total histopathological score was obtained by adding all the scores. In addition, dynamic renal scintigraphy findings were evaluated. Results: Serum parameters indicating inflammation, serum tumor necrosis factoralpha, ischemia modified-albumin, IMA/albumin ratio and Pentraxin-3 levels, were observed to be high in the UPUO group and low in the UPUO/HBO treatment group. Similarly, in the treatment group, the reduction in malondialdehyde, total oxidant status and oxidative stress index levels and increase in total antioxidant capacity values were observed to be statistically significant compared to the UPUO group (p<0.001, p=0.007, p<0.001, p=0.001, respectively). The total score and apoptosis index significantly decreased after administration of HBO treatment. Dynamic 99mTc-MAG3 renal scintigraphy also showed convincing evidence regarding the protective nature of HBO against kidney injury. In the UPUO/HBO therapy group, the percentage contribution of each operated kidney increased significantly compared to the UPUO group (41.73% versus 32.72%). Conclusion:The findings of this study indicate that HBO therapy had a reno-protective effect by reducing inflammation and oxidative stress, and preserving renal function after renal tissue damage due to induction of UPUO.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Sancak¹,

Tan²,

Türkön³

et al. 2017

European Urology Supplements

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“…In our previous experiment, we showed that UUO decreased NO production and that melatonin increased its production. 18 In previous experiments using MSCs in a UUO model, the role of NO was not studied. In the present study, we showed the positive effect of MSCs on NO production in UUO.…”

Section: Discussionmentioning

confidence: 99%

“…The UUO was induced as described previously. 18 The left ureter was isolated and ligated using 3-0 silk sutures. In the MSC group, the UUO surgery was performed, and we injected 1 mL allogeneic MSC and VEGFtransfected MSC suspension (1 × 10 6 cells/mL) into the inferior vena cava 10 minutes after ureteral ligation.…”

Section: Surgical Procedures and Cell Transplantmentioning

confidence: 99%

Untitled

Özbek

Adaş²,

Ötünçtemur³

et al. 2015

Exp Clin Transplant

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Objectives: Mesenchymal stem cells hold promise for renal disease treatment. Vascular endothelial growth factor may heal tubule-interstitial fibrosis in unilateral ureteral obstruction by inhibiting epithelial-mesenchymal transition. We investigated the protective effect of vascular endothelial growth factor in transfected mesenchymal stem cells in unilateral ureteral obstruction-induced renal injury in rats. Materials and Methods: Male Wistar Albino rats (32 rats; weight, 250-300 g) were divided into 4 equal groups: group 1, control; group 2, unilateral ureteral obstruction; group 3, unilateral ureteral obstruction and mesenchymal stem cells; and group 4, unilateral ureteral obstruction and vascular endothelial growth factor-transfected mesenchymal stem cells. Vascular endothelial growth factor-transfected mesenchymal stem cells were administered intravenously before onset of unilateral ureteral obstruction. On day 14, the rats were killed and kidneys were retrieved. Tubular necrosis, mono-nuclear cell infiltration, and interstitial fibrosis were evaluated in paraffin blocks. We evaluated green fluorescent proteinpositive and vascular endothelial growth factorpositive cells; anti-inflammatory (Prostaglandin E2 Receptor) and interleukin 1 receptor antagonist), proinflammatory/anti-inflammatory (interleukin 6), and proinflammatory (MPO) cytokine expression levels; and levels of nitric oxide; transforming growth factor β1, E-cadherin, and hydroxyproline. Results: Green fluorescent protein-positive cells were negative in the renal parenchyma in groups 1 and 2 and positive in groups 3 and 4. Vascular endothelial growth factor levels were significantly higher in group 4. Transforming growth factor β1, nitric oxide, and E-cadherin levels were significantly higher in the unilateral ureteral obstruction than control group; however, in the study groups, these values were not significantly different from the unilateral ureteral obstruction group. In stem celltransplanted tissue samples, EP3, interleukin 1 receptor antagonist, and interleukin 6 levels were elevated, but MPO expression levels were low. Although there were significant differences for tubular necrosis and fibrosis in group 2, there were significant reductions in tubular injury and fibrosis in groups 3 and 4. Conclusions: Systemic stem cells transplanted into the kidney protected against unilateral ureteral obstruction-induced renal epithelial-mesenchymal transition and renal fibrosis.

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“…13,32 Previous studies have shown that melatonin prevents kidney damage by reducing expression of iNOS, and thereby suggested the harm of iNOS. 33 Although its inhibition has been considered as a therapeutic strategy for several disease conditions, 21 few studies have provided experimental evidence in the context of human broses diseases. One study investigated effect of oral administration of iNOS inhibitor FR260330 on liver brosis, 17 and showed this inhibitor could improve liver brosis in rats by inhibiting TGF-b1 production.…”

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confidence: 99%

SKLB023 hinders renal interstitial fibrosis in obstructive nephropathy by interfering TGF-β1/Smad3 signaling

Feng

Guo

et al. 2018

RSC Adv.

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Melatonin Attenuates Unilateral Ureteral Obstruction–Induced Renal Injury by Reducing Oxidative Stress, iNOS, MAPK, and NF-kB Expression

Abstract: MLT may prevent UUO-induced kidney damage in rats by reducing oxidative stress. The mechanism for this is likely mediated via reduction in the expression of iNOS, p38-MAPK, and NF-kB, since MLT reduces the activation of these pathways.

Cited by 75 publications

References 51 publications

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

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

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SKLB023 hinders renal interstitial fibrosis in obstructive nephropathy by interfering TGF-β1/Smad3 signaling

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