scholarly journals Activation of Nrf2 by Ischemic Preconditioning and Sulforaphane in Renal Ischemia/Reperfusion Injury: a Comparative Experimental Study

2015 ◽  
pp. 313-323 ◽  
Author(s):  
A. A. SHOKEIR ◽  
N. BARAKAT ◽  
A. M. HUSSEIN ◽  
A. AWADALLA ◽  
A. M. HARRAZ ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Intercellular Adhesion Molecule ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Antioxidant Genes ◽  
Tnf Α

Objectives of the study were to investigate impact of ischemic preconditioning (Ipre) and sulforaphane (SFN) and combination of them on nuclear factor 2 erythroid related factor 2 (Nrf2) gene and its dependent genes, heme oxygenase-1 (HO1) and NADPH-quinone oxidoreductase1 (NQO-1) and inflammatory cytokines TNF-α, IL1β, and intercellular adhesion molecule-1 (ICAM1) and caspase-3 in renal ischemia/reperfusion (I/R) injury. Ninety male Sprague Dawely rats were classified into 5 groups (each consists of 18 rats): sham, control, Ipre, sulforaphane and Sulfo+Ipre. Each group was subdivided into 3 subgroups each containing 6 rats according to time of harvesting kidney and taking blood samples; 24 h, 48 h, and 7 days subgroups. Renal functions including serum creatinine, BUN were measured at basal conditions and by the end of experiment. Expression of Nrf2, HO-1, NQO-1, TNF-α, IL-1β, and ICAM-1 was measured by real time PCR in kidney tissues by the end of experiment. Also, immunohistochemical localization of caspase-3 and chemical assay of malondialdehyde (MDA), GSH and SOD activity were measured in kidney tissues. Both Ipre and SFN improved kidney functions, enhanced the expression of Nrf2, HO-1, and NQO-1, attenuated the expression of inflammatory (TNF-α, IL-1, and ICAM-1) and apoptotic (caspase-3) markers. However, the effect of sulforaphane was more powerful than Ipre. Also, a combination of them caused more improvement in antioxidant genes expression and more attenuation in inflammatory genes but not caspase-3 than each one did separately. Sulforaphane showed more powerful effect in renoprotection against I/R injury than Ipre as well as there might be a synergism between them at the molecular but not at the function level.

scholarly journals Upregulation of antioxidant nuclear factor erythroid 2-related factor 2 and its dependent genes associated with enhancing renal ischemic preconditioning renoprotection using levosimendan and cilostazol in an ischemia/reperfusion rat model

2021 ◽  
Vol 18 (2) ◽  
pp. 1-34
Author(s):  
Mona Tawfik ◽  
Samy Makary ◽  
Mohammed Keshawy
Keyword(s):  
Ischemic Preconditioning ◽  
Rat Model ◽  
Ischemia Reperfusion ◽  
Blood Oxygenation ◽  
Renal Ischemia ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Quinone Oxidoreductase ◽  
Antioxidant Genes

IntroductionIschemic preconditioning (Ipre) provides protection against renal ischemia-reperfusion (I/R) injury with its associated remote organ damage. This study examined the enhancing protective effect of Ipre with levosimendan or cilostazol in I/R-induced kidney and lung injury in a rat model.Material and methodsRats were divided into: sham-operated, I/R control, Ipre control, I/R + cilostazol or levosimendan and Ipre + cilostazol or levosimendan. Drugs were given 30 min before left renal I/R or 4 cycles of Ipre just before renal ischemia.ResultsThe Ipre combined with the implemented drugs enhanced physio­logical antioxidant defense genes including renal nuclear factor erythroid 2-related factor 2 (Nrf2) and its dependent genes heme oxygenase-1 (HO-1) and NADPH-quinone oxidoreductase-1 (NQO-1) and improved malondialdehyde and superoxide dismutase renal tissue levels. The combined effect improved I/R consequences for blood urea, creatinine, and creatinine clearance and improved blood oxygenation and metabolic acidosis. Moreover, the combination improved the renal soluble intercellular adhesion molecule (ICAM), tumor necrosis factor α (TNF-α) and interlukin-6 (IL-6) with histopathological improvement of tubular necrosis with a decrease in the apoptotic marker caspase-3 and an increase in the anti-apoptotic Bcl-2 expression.ConclusionsCilostazol or levosimendan potentiates the renoprotective effect of Ipre against renal I/R injury, associated with upregulation of antioxidant genes Nrf2, HO-1, and NOQ-1 expression.

scholarly journals Tubeimoside-1 Protects Against Renal Ischemia Reperfusion Injury In Vivo and In Vitro

2020 ◽  
Vol 15 (12) ◽  
pp. 1934578X2097764
Author(s):  
Xiaoli Yuan ◽  
Jing Wang ◽  
Yun Zhang
Keyword(s):  
Reperfusion Injury ◽  
Cell Apoptosis ◽  
Renal Cell ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Caspase 9 ◽  
Tnf Α ◽  
Renal Ischemia Reperfusion Injury

Renal ischemia reperfusion injury (RIRI) is one of the main causes of acute kidney injury. This study aimed to explore whether tubeimoside-1 (TBMS1) could protect against RIRI. RIRI mice model and hypoxia/reoxygenation (H/R)-induced NRK-52E cells were used in this study. The renal pathology was observed by hematoxylin and eosin staining to calculate the tubular injury score. The levels of serum creatinine and blood urine nitrogen were analyzed by a Hitachi model 7180 automatic analyzer. The expressions of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin 6 (IL-6), Bax, cleaved caspase-3, cleaved caspase-9, total caspase-3, and total caspase-9 in renal tissues and NRK-52E cells were detected by western blot analysis. The levels of TNF-α, IL-1β, and IL-6 in serum and NRK-52E cells were measured by a commercial enzyme-linked immunosorbent assay kit. The renal cell apoptosis in renal tissues was analyzed by TUNEL assay, and NRK-52E cell apoptosis was detected by flow cytometry analysis. CCK-8 assay was used to analyze the viability of NRK-52E cells after the indicated treatment. As a result, the renal tissues that were seriously damaged in mice with RIRI could be alleviated by TBMS1. Therefore, 50 mg/kg TBMS1 was chosen for the animal experiment. Renal cell apoptosis was increased in renal tissues of mice with RIRI. These changes could be partially reversed by TBMS1 treatment. TBMS1 improved the viability, and reduced the inflammation and apoptosis of H/R-induced NRK-52E cells. In conclusion, TBMS1 ameliorates RIRI by promoting viability and suppressing apoptosis and inflammation of renal cells.

scholarly journals Ischemic Preconditioning Promotes Autophagy and Alleviates Renal Ischemia/Reperfusion Injury

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ying Xie ◽  
Jing Xiao ◽  
Chensheng Fu ◽  
Zhenxing Zhang ◽  
Zhibin Ye ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Caspase 3 ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Beclin 1 ◽  
Autophagic Flux ◽  
Dependent Manner

Autophagy is important for cellular survival during renal ischemia/reperfusion (I/R) injury. Ischemic preconditioning (IPC) has a strong renoprotective effect during renal I/R. Our study here aimed to explore the effect of IPC on autophagy during renal I/R injury. Rats were subjected to unilateral renal ischemia with or without prior IPC. Hypoxia/reoxygenation (H/R) injury was induced in HK-2 cells with or without prior hypoxic preconditioning (HPC). Autophagy and apoptosis were detected after reperfusion or reoxygenation for different time. The results showed that the levels of LC3II, Beclin-1, SQSTM1/p62, and cleaved caspase-3 were altered in a time-dependent manner during renal I/R. IPC further induced autophagy as indicated by increased levels of LC3II and Beclin-1, decreased level of SQSTM1/p62, and accumulation of autophagosomes compared to I/R groups at corresponding reperfusion time. In addition, IPC reduced the expression of cleaved caspase-3 and alleviated renal cell injury, as evaluated by the levels of serum creatinine (Scr), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) in renal tissues. In conclusion, autophagy and apoptosis are dynamically altered during renal I/R. IPC protects against renal I/R injury and upregulates autophagic flux, thus increasing the possibility for a novel therapy to alleviate I/R-induced acute kidney injury (AKI).

scholarly journals Administration of minocycline ameliorates damage in a renal ischemia/reperfusion injury model

2011 ◽  
Vol 34 (1) ◽  
pp. 55 ◽  
Author(s):  
Dan Xia ◽  
Kezhen Shen ◽  
Weidr Zhong ◽  
Hao Pan
Keyword(s):  
Oxidative Stress ◽  
Renal Dysfunction ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Intercellular Adhesion Molecule ◽  
Caspase 8 ◽  
Intercellular Adhesion Molecule 1 ◽  
Caspase 9

Purpose: The purpose of this study was to investigate the effects of minocycline on the renal dysfunction and injury caused by bilateral ischemia/reperfusion (I/R) of murine kidneys in vivo. Methods: Male C57BL/6 mice were administered minocycline (45 mg/kg i.v.) or saline (0.9%, v/v, NaCl) 36 hours prior to I/R. Mice were subjected to bilateral renal ischemia (35 min) followed by reperfusion (6 hours). Serum creatinine (sCr) and blood urea nitrogen (BUN) levels were measured. Additionally, renal superoxide dismutase (SOD) levels, malondialdehyde (MDA) levels and myeloperoxidase (MPO) activity were determined. The expression of intercellular adhesion molecule-1 (ICAM-1), caspase-3, caspase-8 and caspase-9 was determined using real time RT-PCR and Western blot analysis. Results: Minocycline administration significantly reduced the increases in sCr and BUN caused by I/R, indicating attenuation of renal dysfunction and injury, and reduced histological evidence of renal damage caused by I/R. Minocycline administration also markedly reduced the evidence of oxidative stress (MPO activity, SOD and MDA levels), inflammation (ICAM-1 expression and MPO activity) and apoptosis (caspase-3, caspase-8 and caspase-9 expression) in mouse kidneys subjected to I/R. Conclusion: These findings provide good evidence that minocycline can reduce the renal dysfunction and injury caused by I/R of the kidney. Its mechanism may involve suppression of apoptosis, inflammatory response and oxidative stress.

scholarly journals Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death

2021 ◽  
Vol 22 (5) ◽  
pp. 2234
Author(s):  
Laura Giuseppina Di Pasqua ◽  
Clarissa Berardo ◽  
Marta Cagna ◽  
Roberta Verta ◽  
Debora Collotta ◽  
...  
Keyword(s):  
Cardiac Death ◽  
Caspase 3 ◽  
Metabotropic Glutamate Receptor ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Warm Ischemia ◽  
Related Factor ◽  
Caspase 9 ◽  
Uw Solution ◽  
Tnf Α

We previously demonstrated that the blockade of mGluR5 by 2-methyl-6(phenylethynyl)pyridine (MPEP) reduces both cold and warm ischemia/reperfusion injury. Here we evaluated whether MPEP reduces the hepatic preservation injury in rat livers from cardiac-death-donors (DCDs). Livers from DCD rats were isolated after an in situ warm ischemia (30 min) and preserved for 22 h at 4 °C with UW solution. Next, 10 mg/Kg MPEP or vehicle were administered 30 min before the portal clamping and added to the UW solution (3 µM). LDH released during washout was quantified. Liver samples were collected for iNOS, eNOS, NO, TNF-α, ICAM-1, caspase-3 and caspase-9 protein expression and nuclear factor-erythroid-2-related factor-2 (Nrf2) gene analysis. Lower LDH levels were detected in control grafts versus DCD groups. An increase in eNOS and NO content occurred after MPEP treatment; iNOS and TNF-α content was unchanged. ICAM-1 expression was reduced in the MPEP-treated livers as well as the levels of caspase-3 and caspase-9. Nrf2, oxidative stress-sensitive gene, was recovered to control value by MPEP. These results suggest that MPEP can be used to reclaim DCD livers subjected to an additional period of cold ischemia during hypothermic storage. MPEP protects against apoptosis and increased eNOS, whose overexpression has been previously demonstrated to be protective in hepatic ischemia/reperfusion damage.

scholarly journals Remote ischemic per-conditioning protects against renal ischemia–reperfusion injury via suppressing gene expression of TLR4 and TNF-α in rat model

2019 ◽  
Vol 97 (2) ◽  
pp. 112-119 ◽  
Author(s):  
Firouzeh Gholampour ◽  
Jamshid Roozbeh ◽  
Sahar Janfeshan ◽  
Zeinab Karimi
Keyword(s):  
Reperfusion Injury ◽  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Antioxidant Systems ◽  
Tlr4 Signaling ◽  
Tnf Α ◽  
Renal Ischemia Reperfusion Injury ◽  
Tlr4 Signaling Pathway

The pathogenesis of renal ischemia–reperfusion injury (IRI) involves both inflammatory processes and oxidative stress in the kidney. This study determined whether remote ischemic per-conditioning (RIPerC) is mediated by toll-like receptor 4 (TLR4) signaling pathway in rats. Renal IR injury was induced by occluding renal arteries for 45 min followed by 24 h of reperfusion. RIPerC included 4 cycles of 2 min of ischemia of the left femoral artery followed by 3 min of reperfusion performed at the start of renal ischemia. Rats were divided into sham, IR, and RIPerC groups. At the end of the reperfusion period, urine, blood and tissue samples were gathered. IR created kidney dysfunction, as ascertained by a significant decrease in creatinine clearance and a significant increase in sodium fractional excretion. These changes occurred in concert with a decrease in the activities of glutathione peroxidase, catalase, and superoxide dismutase with an increment in malondialdehyde levels, mRNA expression levels of TLR4 and tumor necrosis factor α (TNF-α), and histological damage in renal tissues. RIPerC treatment diminished all these changes. This study demonstrates that RIPerC has protective effects on the kidney after renal IR, which might be related to the inhibition of the TLR4 signaling pathway and augmentation of antioxidant systems.

Ischemic preconditioning improved renal ischemia/reperfusion injury and hyperglycemia

IUBMB Life ◽  
2018 ◽  
Vol 71 (3) ◽  
pp. 321-329 ◽  
Author(s):  
Jian-Ri Li ◽  
Yen-Chuan Ou ◽  
Chih-Cheng Wu ◽  
Jiaan-Der Wang ◽  
Shih-Yi Lin ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury

Which remote ischemic preconditioning protocol is favorable in renal ischemia-reperfusion injury in the rat?

2020 ◽  
Vol 76 (3) ◽  
pp. 439-451
Author(s):  
Gabor Varga ◽  
Souleiman Ghanem ◽  
Balazs Szabo ◽  
Kitti Nagy ◽  
Noemi Pal ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hematological Parameters ◽  
Renal Ischemia ◽  
Remote Ischemic Preconditioning ◽  
Optimal Timing ◽  
Delayed Effect ◽  
Artery Cannulation ◽  
The Right

BACKGROUND: The optimal timing of remote ischemic preconditioning (RIPC) in renal ischemia-reperfusion (I/R) injury is still unclear. We aimed to compare early- and delayed-effect RIPC with hematological, microcirculatory and histomorphological parameters. METHODS: In anesthetized male CrI:WI Control rats (n = 7) laparotomy and femoral artery cannulation were performed. In I/R group (n = 7) additionally a 45-minute unilateral renal ischemia with 120-minute reperfusion was induced. The right hind-limb was strangulated for 3×10 minutes (10-minute intermittent reperfusion) 1 hour (RIPC-1 group, n = 7) or 24 hour (RIPC-24 group, n = 6) prior to the I/R. Hemodynamic, hematological parameters and organs’ surface microcirculation were measured. RESULTS: Control and I/R group had the highest heart rate (p < 0.05 vs base), while the lowest mean arterial pressure (p < 0.05 vs RIPC-1) were found in the RIPC-24 group. The highest microcirculation values were measured in the I/R group (liver: p < 0.05 vs Control). The leukocyte count increased in I/R group (base: p < 0.05 vs Control), also this group’s histological score was the highest (p < 0.05 vs Control). The RIPC-24 group had a significantly lower score than the RIPC-1 (p = 0.0025 vs RIPC-1). CONCLUSION: Renal I/R caused significant functional and morphological, also in the RIPC groups. According to the histological examination the delayed-effect RIPC method was more effective.

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