scholarly journals Irisin: A Promising Target for Ischemia-Reperfusion Injury Therapy

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Yani Wang ◽  
Huibin Liu ◽  
Na Sun ◽  
Jing Li ◽  
Xiang Peng ◽  
...  

Ischemia-reperfusion injury (IRI) is defined as the total combined damage that occurs during a period of ischemia and following the recovery of blood flow. Oxidative stress, mitochondrial dysfunction, and an inflammatory response are factors contributing to IRI-related damage that can each result in cell death. Irisin is a polypeptide that is proteolytically cleaved from the extracellular domain of fibronectin type III domain-containing protein 5 (FNDC5). Irisin acts as a myokine that potentially mediates beneficial effects of exercise by reducing oxidative stress, improving mitochondrial fitness, and suppressing inflammation. The existing literature also suggests a possible link between irisin and IRI, involving mechanisms similar to those associated with exercise. This article will review the pathogenesis of IRI and the potential benefits and current limitations of irisin as a therapeutic strategy for IRI, while highlighting the mechanistic correlations between irisin and IRI.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yong Li ◽  
Hongbo Zhang ◽  
Zhanhu Li ◽  
Xiaoju Yan ◽  
Yuan Li ◽  
...  

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.


2021 ◽  
Author(s):  
Camila Dossi ◽  
Romina Vargas ◽  
Rodrigo Valenzuela ◽  
Luis Videla

Liver ischemia-reperfusion injury (IRI) is a phenomenon inherent to hepatic surgery that severely compromises the organ functionality, whose underlying mechanisms involve cellular and molecular interrelated processes leading to the development...


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Aleksandra Kezic ◽  
Ivan Spasojevic ◽  
Visnja Lezaic ◽  
Milica Bajcetic

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.


Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1602
Author(s):  
Guangsu Zhu ◽  
Jianxin Zhao ◽  
Hao Zhang ◽  
Wei Chen ◽  
Gang Wang

Psychobiotics are used to treat neurological disorders, including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, the mechanisms underlying their neuroprotective effects remain unclear. Herein, we report that the administration of bifidobacteria in an AD mouse model improved behavioral abnormalities and modulated gut dysbiosis. Bifidobacterium breve CCFM1025 and WX treatment significantly improved synaptic plasticity and increased the concentrations of brain-derived neurotrophic factor (BDNF), fibronectin type III domain-containing protein 5 (FNDC5), and postsynaptic density protein 95 (PSD-95). Furthermore, the microbiome and metabolomic profiles of mice indicate that specific bacterial taxa and their metabolites correlate with AD-associated behaviors, suggesting that the gut–brain axis contributes to the pathophysiology of AD. Overall, these findings reveal that B. breve CCFM1025 and WX have beneficial effects on cognition via the modulation of the gut microbiome, and thus represent a novel probiotic dietary intervention for delaying the progression of AD.


2020 ◽  
Vol 50 (6) ◽  
pp. 1513-1522
Author(s):  
Şenol KALYONCU ◽  
Bülent YILMAZ ◽  
Mustafa DEMİR ◽  
Meltem TUNCER ◽  
Zehra BOZDAĞ ◽  
...  

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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