Effects of Nitroglycerine on Renal Ischemia-Reperfusion Injury in Adult Male Rats

Abstract Background Ischemia-reperfusion (I-R) leads to acute kidney injury (AKI). The present study investigated the effects of nitroglycerine (NG) on improving renal dysfunctions caused by I-R in rats. Methodology Twenty-four rats were equally divided into four groups: (1) the control group, (2) the sham group, (3) the I-R group, and (4) NG-treated groups.NG (50 μg/kg) was injected intraperitoneally after induction of IR. I-R was induced through clamping of the bilateral renal artery and vein of both kidneys for 20 min followed by 24 h of reperfusion. Results NG significantly increased the creatinine clearance levels and renal blood flow rate (which was reduced by I-R). NG also significantly improved serum electrolytes (sodium and potassium) that were disordered by I-R. In addition, NG significantly offset impaired antioxidant defense mechanism and inhibited lipid peroxidation. Conclusions The results show NG has a protective effect on renal tissue against AKI caused by I-R. These protective effects mediated through antioxidant activity and decrease of lipid peroxidation.

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Ascorbic acid improves renal microcirculatory oxygenation in a rat model of renal I/R injury

Journal of Translational Internal Medicine ◽

10.1515/jtim-2015-0011 ◽

2015 ◽

Vol 3 (3) ◽

pp. 116-125 ◽

Cited By ~ 3

Author(s):

Bulent Ergin ◽

Coert J. Zuurbier ◽

Rick Bezemer ◽

Asli Kandil ◽

Emre Almac ◽

...

Keyword(s):

Oxidative Stress ◽

Ascorbic Acid ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Renal Tissue ◽

Control Group ◽

Free Oxygen Radicals ◽

Time Control ◽

Inflammatory Parameters

AbstractBackground and objectives: Acute kidney injury (AKI) is a clinical condition associated with a degree of morbidity and mortality despite supportive care, and ischemia/reperfusion injury (I/R) is one of the main causes of AKI. The pathophysiology of I/R injury is a complex cascade of events including the release of free oxygen radicals followed by damage to proteins, lipids, mitochondria, and deranged tissue oxygenation. In this study, we investigated whether the antioxidant ascorbic acid would be able to largely prevent oxidative stress and consequently, reduce I/R-related injury to the kidneys in terms of oxygenation, inflammation, and renal failure. Materials and methods: Rats were divided into three groups (n = 6/group): (1) a time control group; (2) a group subjected to renal ischemia for 60 min by high aortic occlusion followed by 2 h of reperfusion (I/R); and (3) a group subjected to I/R and treated with an i.v. 100 mg/kg bolus ascorbic acid 15 min before ischemia and continuous infusion of 50 mg/kg/hour for 2 h during reperfusion (I/R + AA). We measured renal tissue oxidative stress, microvascular oxygenation, renal oxygen delivery and consumption, and renal expression of inflammatory and injury markers. Results: We demonstrated that aortic clamping and release resulted in increased oxidative stress and inflammation that was associated with a significant fall in systemic and renal hemodynamics and oxygenation parameters. The treatment of ascorbic acid completely abrogated oxidative stress and inflammatory parameters. However, it only partly improved microcirculatory oxygenation and was without any effect on anuria. Conclusion: The ascorbic acid treatment partly improves microcirculatory oxygenation and prevents oxidative stress without restoring urine output in a severe I/R model of AKI.

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Protective Effects Of Trimetazidine Against Hepatic Warm Ischemia/Reperfusion Injury On Rats

Journal of Experimental and Clinical Medicine ◽

10.52142/omujecm.38.2.3 ◽

2021 ◽

Vol 38 (2) ◽

pp. 66-71

Author(s):

Tevfik NOYAN ◽

Sertaç AYHAN ◽

Sevil IŞIK ◽

Sibel KÖKTÜRK

Keyword(s):

Fatty Liver ◽

Structural Integrity ◽

Defense Mechanism ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Warm Ischemia ◽

Male Rats ◽

Control Group ◽

Group 3

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver diseases that occur in individuals who do not consume a significant amount of alcohol, and the pathogenesis of NAFLD remains undefined. It was aimed to investigate whether the use of Trimetazidine (TMZ) could reduce warm ischemia-reperfusion (I/R) damage after liver ischemia on an experimental NAFLD model in this experimental study. Methods: For this aim, Sprague Dawley male rats were separated into 4 groups; control group (group 1, n = 6), sham operated control grup (group 2, n = 6), warm ischemia/reperfusion group (group 3, n=10), and TMZ group (group 4, n=10, administration of TMZ (10 mg/kg) 30-min before fatty liver I/R). The serum oxidant and antioxidant biochemical markers were measured by ELISA methods. The histopathological evaluation was also performed in the hepatocytes. Results: TMZ was caused to significantly decrease on oxidative stress markers levels which characterized myeloperoxidase (MPO) (p<0.001), nicotinamide adenine dinucleotide phosphate-oxidase (NOX) (p<0.001), and cytochrome C (Cyt-C) (p<0.001), and increase on antioxidant enzyme catalase (CAT) (p<0.001) activity as compared to group 3. However, TMZ was no caused to any significant change in other oxidant markers malondialdehyde (MDA) and 8-hydroxyguanosine (8-OHDG) levels (p> 0.05). While hepatocyte damage as a form of cell groups was observed due to I/R damage, whereas TMZ had caused positive improvements on dilatation of sinusoids, inflammation and the structural integrity of hepatic plaques. Conclusion: Trimetazidine could be positively contributing effects to the antioxidant defense mechanism and also the survival of cells by protecting mitochondrial integrity.

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Comparison of protective effects of trimetazidine against experimental warm ischemia of different durations: early and long-term effects in a pig kidney model

AJP Renal Physiology ◽

10.1152/ajprenal.00338.2006 ◽

2007 ◽

Vol 292 (3) ◽

pp. F1082-F1093 ◽

Cited By ~ 38

Author(s):

Christophe Jayle ◽

Frederic Favreau ◽

Kequiang Zhang ◽

Carole Doucet ◽

Jean Michel Goujon ◽

...

Keyword(s):

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Warm Ischemia ◽

Control Group ◽

Protective Effects ◽

Long Term Effects ◽

Tissue Destruction ◽

Pig Kidney

Acute renal failure (ARF) is often the consequence of an ischemia-reperfusion injury (IRI) and associated with high mortality. Warm ischemia (WI) is a crucial factor of tissue damage, and tissue destruction led by ischemia-reperfusion (I/R) can impact the early and long-term functional outcome. Trimetazidine (TMZ) is an anti-ischemic drug. Previously, we already verified its protective effect on a cold-ischemic pig kidney model by directly adding TMZ into the preservation solution (Faure JP, Baumert H, Han Z, Goujon JM, Favreau F, Dutheil D, Petit I, Barriere M, Tallineau C, Tillement JP, Carretier M, Mauco G, Papadopoulos V, Hauet T. Biochem Pharmacol 66: 2241–2250, 2003; Faure JP, Petit I, Zhang K, Dutheil D, Doucet C, Favreau F, Eugene M, Goujon JM, Tillement JP, Mauco G, Vandewalle A, Hauet T. Am J Transplant 4: 495–504, 2004). In this study, we aimed to study the potential effect of TMZ pretreatment (5 mg/kg iv 24 h before WI) on the injury caused by WI for 45, 60, and 90 min and reperfusion in a WI pig kidney model. Compared with sham-operated (control) and uninephrectomized animals (UNX), TMZ pretreatment significantly reduced deleterious effects after 45 min, and particularly 60 and 90 min, of WI by improving the recovery of renal function and minimizing the inflammatory response commonly prevalent in ischemic kidney injury. Compared with controls (control group and UNX group), it was observed that 1) hypoxia-inducible factor-1 (HIF-1α) expression occurred earlier and with a higher intensity in the TMZ-treated groups; 2) the reduction of IRI during the first week following reperfusion was correlated with an earlier and greater expression of stathmin, which is involved in the process of tubular repair; and 3) the tubulointerstitial fibrosis was reduced, particularly after 60 and 90 min of WI. In conclusion, TMZ made the warm-ischemic kidneys more resistant to the deleterious impact of a single episode of I/R and reduced early and long-term subsequent damage.

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Kaempferol Ameliorates Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Ferroptosis by Activating Nrf2/SLC7A11/GPX4 Axis

Biomolecules ◽

10.3390/biom11070923 ◽

2021 ◽

Vol 11 (7) ◽

pp. 923

Author(s):

Yuan Yuan ◽

Yanyu Zhai ◽

Jingjiong Chen ◽

Xiaofeng Xu ◽

Hongmei Wang

Keyword(s):

Lipid Peroxidation ◽

Cell Death ◽

Antioxidant Capacity ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

Related Factor ◽

Protective Effects

Kaempferol has been shown to protect cells against cerebral ischemia/reperfusion injury through inhibition of apoptosis. In the present study, we sought to investigate whether ferroptosis is involved in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal injury and the effects of kaempferol on ferroptosis in OGD/R-treated neurons. Western blot, immunofluorescence, and transmission electron microscopy were used to analyze ferroptosis, whereas cell death was detected using lactate dehydrogenase (LDH) release. We found that OGD/R attenuated SLC7A11 and glutathione peroxidase 4 (GPX4) levels as well as decreased endogenous antioxidants including nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and superoxide dismutase (SOD) in neurons. Notably, OGD/R enhanced the accumulation of lipid peroxidation, leading to the induction of ferroptosis in neurons. However, kaempferol activated nuclear factor-E2-related factor 2 (Nrf2)/SLC7A11/GPX4 signaling, augmented antioxidant capacity, and suppressed the accumulation of lipid peroxidation in OGD/R-treated neurons. Furthermore, kaempferol significantly reversed OGD/R-induced ferroptosis. Nevertheless, inhibition of Nrf2 by ML385 blocked the protective effects of kaempferol on antioxidant capacity, lipid peroxidation, and ferroptosis in OGD/R-treated neurons. These results suggest that ferroptosis may be a significant cause of cell death associated with OGD/R. Kaempferol provides protection from OGD/R-induced ferroptosis partly by activating Nrf2/SLC7A11/GPX4 signaling pathway.

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The protective effects of pomegranate extracts against renal ischemia-reperfusion injury in male rats

Urology Annals ◽

10.4103/0974-7796.127029 ◽

2014 ◽

Vol 6 (1) ◽

pp. 46 ◽

Cited By ~ 12

Author(s):

AhmetA Sancaktutar ◽

MehmetN Bodakci ◽

NamıkK Hatipoglu ◽

Kemal Basarılı ◽

Haluk Soylemez ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Renal Ischemia ◽

Male Rats ◽

Protective Effects ◽

Renal Ischemia Reperfusion Injury

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Urinary N-Acetyl-Beta-D-Glucosaminidase Activity in Rat Experimental Ischemic and Toxic Models of Acute Kidney Injury

Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca Veterinary Medicine ◽

10.15835/buasvmcn-vm:12618 ◽

2017 ◽

Vol 74 (1) ◽

pp. 105

Author(s):

Razvan Andrei CODEA ◽

Mircea MIRCEAN ◽

Sidonia Alina BOGDAN ◽

Andras Laszlo NAGY ◽

Alexandra BIRIS ◽

...

Keyword(s):

Acute Kidney Injury ◽

Experimental Model ◽

Wistar Rats ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Control Group ◽

Tubular Injury ◽

Group 2 ◽

Group 1

The identification of a suitable prevention method which facilitates limiting the deleterious effects of acute kidney injuries is highly required. In order to identify a proper treatment for acute kidney injuries, a suitable experimental model that replicates the structural, metabolic and inflammatory lesions that occur in the natural acute injured kidney is highly necessary. Intense urinary NAG activity can be found in a variety of renal disease such as toxic nephropathies, ischemic renal injury following cardiac surgery or renal transplantation but also in glomerular disease especially in diabetic nephropathy. Rises in urinary NAG enzyme activity strongly suggests tubular cell damage and support NAG enzyme as a biomarker of renal tubular injury. The aim of this paper is to obtain a stable in vivo acute kidney injury experimental model, in Wistar, rats and to evaluate the urinary activity of N-acetyl-Î²-D-glucosaminidase (NAG) enzyme, blood levels of urea and creatinine and microstructural renal alterations induced by ischemia/reperfusion injury respectively gentamicin nephrotoxicity. For this purpose we have used a rat experimental model. Adult male Wistar rats weighing 250-300 g were randomly divided into 3 groups with 8 rats in each group. Group 1 served as a model for the renal ischemia/reperfusion injury experiment, group 2 served for toxic kidney injury experimental model and group 3 served as control group. All individuals in both groups 1 and 2 presented marked elevations in blood urea and creatinine at the moment of euthanasia (day 3 for group 1 and day 9 for group 2) compared to the control group where biochemical values remained within normal limits. Urine analysis of both group 1 and 2 showed marked urinary NAG index activity which suggests acute tubular injury, suggestion confirmed by histological evaluation of the renal parenchyma sampled from this subjects

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Molecular Mechanisms of Renal Ischemic Conditioning Strategies

European Surgical Research ◽

10.1159/000437352 ◽

2015 ◽

Vol 55 (3) ◽

pp. 151-183 ◽

Cited By ~ 12

Author(s):

Casper Kierulf-Lassen ◽

Gertrude J. Nieuwenhuijs-Moeke ◽

Nicoline V. Krogstrup ◽

Mihai Oltean ◽

Bente Jespersen ◽

...

Keyword(s):

Reperfusion Injury ◽

Molecular Mechanisms ◽

Defense Mechanism ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Clinical Settings ◽

Ischemic Conditioning ◽

Protective Signaling ◽

Survival Mechanisms

Ischemia-reperfusion injury is the leading cause of acute kidney injury in a variety of clinical settings such as renal transplantation and hypovolemic and/or septic shock. Strategies to reduce ischemia-reperfusion injury are obviously clinically relevant. Ischemic conditioning is an inherent part of the renal defense mechanism against ischemia and can be triggered by short periods of intermittent ischemia and reperfusion. Understanding the signaling transduction pathways of renal ischemic conditioning can promote further clinical translation and pharmacological advancements in this era. This review summarizes research on the molecular mechanisms underlying both local and remote ischemic pre-, per- and postconditioning of the kidney. The different types of conditioning strategies in the kidney recruit similar powerful pro-survival mechanisms. Likewise, renal ischemic conditioning mobilizes many of the same protective signaling pathways as in other organs, but differences are recognized.

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Pretreatment Donors after Circulatory Death with Simvastatin Alleviates Liver Ischemia Reperfusion Injury through a KLF2-Dependent Mechanism in Rat

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/3861914 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Zhongzhong Liu ◽

Xingjian Zhang ◽

Qi Xiao ◽

Shaojun Ye ◽

Chin-Hui Lai ◽

...

Keyword(s):

Reperfusion Injury ◽

Target Genes ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Male Rats ◽

Control Group ◽

Isolated Perfused Rat Liver ◽

Enzyme Release ◽

Circulatory Death ◽

Dependent Mechanism

Objective. Severe hepatic ischemia reperfusion injury (IRI) can result in poor short- and long-term graft outcome after transplantation. The way to improve the viability of livers from donors after circulatory death (DCD) is currently limited. The aim of the present study was to explore the protective effect of simvastatin on DCD livers and investigate the underlying mechanism. Methods. 24 male rats randomly received simvastatin or its vehicle. 30 min later, rat livers were exposed to warm ischemia in situ for 30 min. Livers were removed and cold-stored in UW solution for 24 h, subsequently reperfused for 60 min with an isolated perfused rat liver system. Liver injury was evaluated during and after warm reperfusion. Results. Pretreatment of DCD donors with simvastatin significantly decreased IRI liver enzyme release, increased bile output and ATP, and ameliorated hepatic pathological changes. Simvastatin maintained the expression of KLF2 and its protective target genes (eNOS, TM, and HO-1), reduced oxidative stress, inhibited innate immune responses and inflammation, and increased the expression of Bcl-2/Bax to suppress hepatocyte apoptosis compared to DCD control group. Conclusion. Pretreatment of DCD donors with simvastatin improves DCD livers’ functional recovery probably through a KLF2-dependent mechanism. These data suggest that simvastatin may provide a potential benefit for clinical DCD liver transplantation.

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Ischemic preconditioning and morphine attenuate myocardial apoptosis and infarction after ischemia-reperfusion in rabbits: role of δ-opioid receptor

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01143.2003 ◽

2004 ◽

Vol 287 (4) ◽

pp. H1786-H1791 ◽

Cited By ~ 42

Author(s):

Shinji Okubo ◽

Yujirou Tanabe ◽

Kenji Takeda ◽

Michihiko Kitayama ◽

Seiyu Kanemitsu ◽

...

Keyword(s):

Infarct Size ◽

Opioid Receptor ◽

Ischemic Preconditioning ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Terminal Deoxynucleotidyl Transferase ◽

Control Group ◽

Apoptotic Cells ◽

Protective Effects ◽

Δ Opioid Receptor

We examined whether ischemic preconditioning (IPC) attenuates ischemia-reperfusion injury, in part, by decreasing apoptosis and whether the δ-opioid receptor (DOR) plays a pivotal role in the regulation of apoptosis. Rabbits were subjected to 30-min coronary artery occlusion (CAO) and 180 min of reperfusion. IPC was elicited with four cycles of 5-min ischemia and 10-min reperfusion before CAO. Morphine (0.3 mg/kg iv) was given 15 min before CAO. Naloxone (Nal; 10 mg/kg iv) and naltrindole (Nti; 10 mg/kg iv), the respective nonselective and selective DOR antagonists were given 10 min before either morphine or IPC. Infarct size (%risk area) was reduced from 46 ± 3.8 in control to 11.6 ± 1.0 in IPC and 19.5 ± 3.8 in the morphine group (means ± SE; P < 0.001 vs. control). Nal blocked the protective effects of IPC and morphine, as shown by the increase in infarct size to 38.6 ± 7.2 and 44.5 ± 1.8, respectively. Similarly, Nti blocked IPC and morphine-induced protection. The percentage of apoptotic cells (revealed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) decreased in IPC (3.6 ± 1.9) and morphine groups (5.2 ± 1.2) compared with control group (12.4 ± 1.6; P < 0.001). Nti pretreatment increased apoptotic cells 11.2 ± 2.2% in IPC and 12.1 ± 0.8% in morphine groups. Nal failed to block inhibition of apoptosis in the IPC group (% of cells: 5.7 ± 1.3 vs. 3.6 ± 1.9 in IPC alone; P > 0.05). These results were also confirmed by nucleosomal DNA laddering pattern. We conclude that IPC reduces lethal injury, in part, by decreasing apoptosis after ischemia-reperfusion and activation of the DOR may play a crucial role in IPC or morphine-induced myocardial protection.

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Cell Death Patterns Due to Warm Ischemia or Reperfusion in Renal Tubular Epithelial Cells Originating from Human, Mouse, or the Native Hibernator Hamster

Biology ◽

10.3390/biology7040048 ◽

2018 ◽

Vol 7 (4) ◽

pp. 48 ◽

Cited By ~ 5

Author(s):

Theodoros Eleftheriadis ◽

Georgios Pissas ◽

Georgia Antoniadi ◽

Vassilios Liakopoulos ◽

Ioannis Stefanidis

Keyword(s):

Lipid Peroxidation ◽

Acute Kidney Injury ◽

Cell Death ◽

Epithelial Cells ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Human Cells ◽

Tubular Epithelial Cells

Ischemia–reperfusion injury contributes to the pathogenesis of many diseases, with acute kidney injury included. Hibernating mammals survive prolonged bouts of deep torpor with a dramatic drop in blood pressure, heart, and breathing rates, interspersed with short periods of arousal and, consequently, ischemia–reperfusion injury. Clarifying the differences under warm anoxia or reoxygenation between human cells and cells from a native hibernator may reveal interventions for rendering human cells resistant to ischemia–reperfusion injury. Human and hamster renal proximal tubular epithelial cells (RPTECs) were cultured under warm anoxia or reoxygenation. Mouse RPTECs were used as a phylogenetic control for hamster cells. Cell death was assessed by both cell imaging and lactate dehydrogenase (LDH) release assay, apoptosis by cleaved caspase-3, autophagy by microtubule-associated protein 1-light chain 3 B II (LC3B-II) to LC3B-I ratio, necroptosis by phosphorylated mixed-lineage kinase domain-like pseudokinase, reactive oxygen species (ROS) fluorometrically, and lipid peroxidation, the end-point of ferroptosis, by malondialdehyde. Human cells died after short periods of warm anoxia or reoxygenation, whereas hamster cells were extremely resistant. In human cells, apoptosis contributed to cell death under both anoxia and reoxygenation. Although under reoxygenation, ROS increased in both human and hamster RPTECs, lipid peroxidation-induced cell death was detected only in human cells. Autophagy was observed only in human cells under both conditions. Necroptosis was not detected in any of the evaluated cells. Clarifying the ways that are responsible for hamster RPTECs escaping from apoptosis and lipid peroxidation-induced cell death may reveal interventions for preventing ischemia–reperfusion-induced acute kidney injury in humans.

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