scholarly journals Custodiol® Supplemented with Synthetic Human Relaxin Decreases Ischemia-Reperfusion Injury after Porcine Kidney Transplantation

2021 ◽  
Vol 22 (21) ◽  
pp. 11417
Author(s):  
Augustinas Bausys ◽  
Juste Maneikyte ◽  
Bettina Leber ◽  
Jennifer Weber ◽  
Nicole Feldbacher ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Peptide Hormone ◽  
Pcr Analysis ◽  
Large Animal ◽  
Large Animal Models

Objective. Ischemia-reperfusion injury (IRI) is inevitable after kidney transplantation (KT), impairing outcomes. Relaxin-2 (RLX) is a promising insulin-related peptide hormone that protects against renal IRI in rodents, although large animal models are needed before RLX can be tested in a human setting. Methods. In this blinded, randomized, and placebo-controlled experimental study kidneys from 19 donor pigs were retrieved after perfusion with Custodiol® ± RLX (5 or 20 nmol/L) and underwent static cold storage (SCS) for 24 and 48 h, respectively. Subsequently, KT was performed after unilateral right nephrectomy. Study outcomes included markers for kidney function, oxidative stress, lipid peroxidation, and endothelial cell damage. PCR analysis for oxidative stress and apoptosis-related gene panels as well as immunohistochemistry were performed. Results. RLX upregulated SOD2 and NFKB expression to 135% (p = 0.042) and 125% (p = 0.019), respectively, while RIPK1 expression was downregulated to 82% (p = 0.016) of corresponding controls. Further RLX significantly downregulated RIPK1 and MLKL expression and decreased the number of Caspase 3- and MPO-positive cells in grafts after SCS. Conclusions. RLX supplemented Custodiol® significantly decreased IRI via both antioxidant and anti-apoptotic mechanisms. Clinical trials are warranted to implement synthetic human RLX as a novel additive to preservation solutions against IRI.

scholarly journals microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yong Li ◽  
Hongbo Zhang ◽  
Zhanhu Li ◽  
Xiaoju Yan ◽  
Yuan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Mouse Models ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Gene Assay ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Background Myocardial ischemia reperfusion injury (MIRI) is defined as tissue injury in the pathological process of progressive aggravation in ischemic myocardium after the occurrence of acute coronary artery occlusion. Research has documented the involvement of microRNAs (miRs) in MIRI. However, there is obscure information about the role of miR-130a-5p in MIRI. Herein, this study aims to investigate the effect of miR-130a-5p on MIRI. Methods MIRI mouse models were established. Then, the cardiac function and hemodynamics were detected using ultrasonography and multiconductive physiological recorder. Functional assays in miR-130a-5p were adopted to test the degrees of oxidative stress, mitochondrial functions, inflammation and apoptosis. Hematoxylin and eosin (HE) staining was performed to validate the myocardial injury in mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression patterns of miR-130a-5p, high mobility group box (HMGB)2 and NF-κB. Then, dual-luciferase reporter gene assay was performed to elucidate the targeting relation between miR-130a-5p and HMGB2. Results Disrupted structural arrangement in MIRI mouse models was evident from HE staining. RT-qPCR revealed that overexpressed miR-130a-5p alleviated MIRI, MIRI-induced oxidative stress and mitochondrial disorder in the mice. Next, the targeting relation between miR-130a-5p and HMGB2 was ascertained. Overexpressed HMGB2 annulled the protective effects of miR-130a-5p in MIRI mice. Additionally, miR-130a-5p targets HMGB2 to downregulate the nuclear factor kappa-B (NF-κB) axis, mitigating the inflammatory injury induced by MIRI. Conclusion Our study demonstrated that miR-130a-5p suppresses MIRI by down-regulating the HMGB2/NF-κB axis. This investigation may provide novel insights for development of MIRI treatments.

scholarly journals Mitochondria-Targeted Antioxidants: Future Perspectives in Kidney Ischemia Reperfusion Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Aleksandra Kezic ◽  
Ivan Spasojevic ◽  
Visnja Lezaic ◽  
Milica Bajcetic
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Current Status ◽  
Long Time ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Kidney Ischemia

Kidney ischemia/reperfusion injury emerges in various clinical settings as a great problem complicating the course and outcome. Ischemia/reperfusion injury is still an unsolved puzzle with a great diversity of investigational approaches, putting the focus on oxidative stress and mitochondria. Mitochondria are both sources and targets of ROS. They participate in initiation and progression of kidney ischemia/reperfusion injury linking oxidative stress, inflammation, and cell death. The dependence of kidney proximal tubule cells on oxidative mitochondrial metabolism makes them particularly prone to harmful effects of mitochondrial damage. The administration of antioxidants has been used as a way to prevent and treat kidney ischemia/reperfusion injury for a long time. Recently a new method based on mitochondria-targeted antioxidants has become the focus of interest. Here we review the current status of results achieved in numerous studies investigating these novel compounds in ischemia/reperfusion injury which specifically target mitochondria such as MitoQ, Szeto-Schiller (SS) peptides (Bendavia), SkQ1 and SkQR1, and superoxide dismutase mimics. Based on the favorable results obtained in the studies that have examined myocardial ischemia/reperfusion injury, ongoing clinical trials investigate the efficacy of some novel therapeutics in preventing myocardial infarct. This also implies future strategies in preventing kidney ischemia/reperfusion injury.

scholarly journals Melatonin attenuates ovarian ischemia reperfusion injury in rats by decreasing oxidative stress index and peroxynitrite

2020 ◽  
Vol 50 (6) ◽  
pp. 1513-1522
Author(s):  
Şenol KALYONCU ◽  
Bülent YILMAZ ◽  
Mustafa DEMİR ◽  
Meltem TUNCER ◽  
Zehra BOZDAĞ ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Stress Index ◽  
Oxidative Stress Index ◽  
Group 6 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background/aim: To evaluate the protective effect of melatonin on ovarian ischemia reperfusion injury in a rat model. Materials and methods: Forty-eight rats were separated equally into 6 groups. Group 1: sham; Group 2: surgical control with 3-h bilateral ovarian torsion and detorsion; Group 3: intraperitoneal 5% ethanol (1 mL) just after detorsion (as melatonin was dissolved in ethanol); Group 4: 10 mg/kg intraperitoneal melatonin 30 min before 3-h torsion; Group 5:10 mg/kg intraperitoneal melatonin just after detorsion; Group 6:10 mg/kg intraperitoneal melatonin 30 min before torsion and just after detorsion. Both ovaries and blood samples were obtained 7 days after detorsion for histopathological and biochemical analysis.Results: In Group 1, serum levels of total oxidant status (TOS) (μmol H2O2 equivalent/g wet tissue)were significantly lower than in Group2 (P = 0.0023), while tissue TOS levels were lower than in Group 3 (P = 0.0030). Similarly, serum and tissue levels of peroxynitrite in Group 6were significantly lower than those ofGroup 2 (P = 0.0023 and P = 0.040, respectively). Moreover, serum oxidative stress index (OSI) (arbitrary unit) levels were significantly increased in Group 2 when compared to groups 1 and 6 (P = 0.0023 and P= 0.0016, respectively) and in Group 3 with respect to groups 1, 4, 5, and 6 (P = 0.0023, P = 0.0026, P = 0.0008, and P = 0.0011, respectively). Furthermore, there was a significant decrease in histopathological scores including follicular degeneration, vascular congestion, hemorrhage, and inflammation in the melatonin and sham groups in comparison with control groups. Additionally, primordial follicle count was significantly higher in Group 6 than in Group 2 (P = 0.0002).Conclusion: Melatonin attenuates ischemia reperfusion damage in a rat torsion/detorsion model by improving histopathological and biochemical findings including OSI and peroxynitrite.

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