Ischemia-reperfusion Damage Research Articles

LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in Cardiomyocytes.

Objective: Myocardial ischemia reperfusion (I/R) damage is a life-threatening vascular emergency after myocardial infarction. Here, we observed the cardioprotective effect of long non-coding RNA (lncRNA) PVT1 knockdown against myocardial I/R damage.Methods: This study constructed a myocardial I/R-induced mouse model and a hypoxia/reoxygenation (H/R)-treated H9C2 cells. PVT1 expression was examined via RT-qPCR. After silencing PVT1 via shRNA against PVT1, H&E, and Masson staining was performed to observe myocardial I/R damage. Indicators of myocardial injury including cTnI, LDH, BNP, and CK-MB were examined by ELISA. Inflammatory factors (TNF-α, IL-1β, and IL-6), Gasdermin D (GSDMD), and Caspase1 were detected via RT-qPCR, western blot, immunohistochemistry, or immunofluorescence. Furthermore, CCK-8 and flow cytometry were presented for detecting cell viability and apoptosis.Results: LncRNA PVT1 was markedly up-regulated in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Silencing PVT1 significantly lowered serum levels of cTnI, LDH, BNP, and CK-MB in myocardial I/R mice. H&E and Masson staining showed that silencing PVT1 alleviated myocardial I/R injury. PVT1 knockdown significantly lowered the production and release of inflammatory factors as well as inhibited the expression of GSDMD-N and Caspase1 in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Moreover, silencing PVT1 facilitated cell viability and induced apoptosis of H/R-treated H9C2 cells.Conclusion: Our findings demonstrated that silencing PVT1 could alleviate myocardial I/R damage through suppressing GSDMD-mediated pyroptosis in vivo and in vitro. Thus, PVT1 knockdown may offer an alternative therapeutic strategy against myocardial I/R damage.

Рання та відстрочена реакція білка Hif-1α в полях гіпокампа на ішемію-реперфузію в щурів зі стрептозотоцин-індукованим цукровим діабетом

Актуальність. Роль транскрипційного фактора Hif-1α в патогенезі гіпоксичних ушкоджень та цукрового діабету (ЦД) доведена, однак молекулярні механізми, що лежать в основі дисфункції даного фактора при поєднанні ЦД з ішемічно-реперфузійним ушкодженням головного мозку, залишаються нез’ясованими. Мета. Вивчення вмісту білка Hif-1α в нейронах полів гіпокампа щурів з експериментальним ЦД у динаміці ішемічно-реперфузійного ушкодження головного мозку. Матеріали та методи. Дослідження виконано на 6-місячних щурах, яким у віці два місяці моделювали ЦД однократним уведенням стрептозотоцину (60 мг/кг маси тіла) (Sigma, США). Порушення мозкового кровообігу відтворювали шляхом оклюзії обох сонних артерій протягом 20 хвилин. Уміст білка Hif1-α визначали методом імунофлуоресценції після 20-хвилинної ішемії з одногодинною реперфузією та на 12-ту добу постішемічного періоду в полях гіпокампа СА1, СА2, СА3, СА4. Результати. У щурів без ЦД 20-хвилинна ішемія з одногодинною реперфузією підвищує вміст білка Hif-1α в усіх досліджених полях гіпокампа. На 12-ту добу ішемічно-реперфузійного періоду в полях гіпокампа СА2-СА4 значення окремих досліджених показників активності транскрипційного фактора Hif-1α продовжують зростати, а в полі СА1 — нормалізуються або наближаються до значень у тварин конт­рольної групи. У щурів із ЦД у ранньому постішемічному періоді в полі СА1 зміни вмісту білка Hif-1α відсутні, в полі СА2 наявні ознаки зниження його активності, в полі СА3 — обмежені реакцією одного показника, в полі СА4 мають такий же характер, як і в контрольних щурів, за даних експериментальних умов. На 12-ту добу ішемічно-реперфузійного періоду в полі СА1 зростають усі показники активності транскрипційного фактора Hif-1α, за абсолютними значеннями перевищуючи відповідні у тварин контрольної групи за тих же експериментальних умов; в полі СА2 і СА3 зміни досліджених параметрів обмежені порівняно з такими у тварин групи контролю; в полі СА4 знижуються показники, які у тварин групи контролю зазнали зростання. Висновки. ЦД обмежує реакцію білка Hif-1α на ішемію-реперфузію в нейронах полів СА1-СА3 у ранньому ішемічно-реперфузійному періоді та в нейронах полів СА2-СА4 — на 12-ту добу спостереження.

Azathioprine pretreatment ameliorates myocardial ischaemia reperfusion injury in diabetic rats by reducing oxidative stress, apoptosis, and inflammation.

This study was presented to observe the therapeutic effects of azathioprine (AZA) pretreatment on myocardial ischaemia reperfusion (I/R) damage in diabetic rats. All rats were randomly separated into control + sham operation; control +I/R; diabetes mellitus (DM) +I/R and DM +I/R + AZA groups. Diabetic rat models were established by intraperitoneally injecting 60 mg/kg streptozotocin (STZ). Diabetic rats were given 3 mg/kg AZA daily by gavage for 5 days. Then, myocardial I/R rat models were constructed. Myocardial infarction size and myocardial damage were respectively detected by TTC and H&E staining. Cardiac injury markers (CK‐MB and MPO) and oxidative stress factors (SOD and MDA) were measured via ELISA. The protein expression of apoptotic markers (Caspase8, Caspase3, BAX and Bcl2), inflammatory factors (TLR4 and TNF‐α) and AKT1/GSK3β in myocardial tissues was measured by western blot, immunohistochemistry or immunofluorescence. Data showed that AZA pretreatment could lessen myocardial infarction size and myocardial damage, and could down‐regulate serum CK‐MB, MPO, SOD and MDA levels in diabetic rats under I/R. Furthermore, AZA pretreatment decreased Caspase8, Caspase3, BAX, TLR4 and TNF‐α expression, and increased Bcl2 expression in myocardial tissues of diabetic rats following I/R. Also, AZA pretreatment lowered AKT1, p‐AKT1, GSK3β and p‐GSK3β expression in diabetic heart after I/R. This study found that AZA may reduce myocardial injury in diabetic rats following I/R via reducing oxidative stress, cardiomyocyte apoptosis, and inflammatory response, which could be related to AKT1/GSK3β pathway inactivation.

Effect of Sunitinib on Liver Oxidative and Proinflammatory Damage Induced by Ischemia-Reperfusion in Rats

Ischemia-reperfusion (IR) injury is defined as a complex pathologic process that begins with the oxygen deprivation of tissue, continues with the production of reactive oxygen radicals (ROS), and expands with an inflammatory response. This study investigates the protective effects of sunitinib, an anticancer drug with demonstrated antioxidant and anti-inflammatory activity, against liver IR damage. Our study aims to investigate the biochemical and histopathologic effects of sunitinib on IR-induced liver damage in rats. Albino Wistar male rats were divided into 3 groups: liver IR control (IR), 25 mg/kg sunitinib+liver IR (S+IR), and sham operation (SHAM). In the liver tissue of the IR group, oxidant and proinflammatory cytokine levels such as malondialdehyde, nuclear factor κ B, tumor necrosis factor-α, and interleukin-1β increased compared with the SHAM and S+IR groups. In addition, antioxidant levels such as total glutathione, glutathione reductase, and glutathione peroxidase were found to be significantly lower in the IR group than in the SHAM and S+IR groups. Although severe histopathologic damage was observed in the IR group, it was evaluated as mild in the S+IR group. The results obtained suggest that sunitinib may be helpful in the treatment of liver IR injury.

An investigation of the effects of amniotic fluid on experimental ischemia/reperfusion damage in rat testes

Various agents have been tested as preventive treatments for ischemia/reperfusion (IR) damage. In this study, we have investigated for the first time in the literature the efficacy of injection of amniomax (AMX) into testicular parenchyma, which is a commercial medium of rat amniotic fluid, in preventing testicular IR damage related to testicular torsion. This study aims to evaluate whether or not amniomax has an effect on experimental IR damage in rat testes using biochemical and histopathological methods based on data in the literature. Even if testicular torsion is repaired surgically in early term injury because of de IR damage still occurs. Is it possible to reduce the ischemia reperfusion injury with amniotic fluid and increase the success of treatment? 40 male Wistar albino rats were included. Four groups were formed with 10 rats in each group: Sham, Ischemia/Reperfusion (IR), injection 1min before detorsion (AMX-BD), injection 1min after detorsion (AMX-AD). Total Oxidant Status (TOS) and Oxidative Stress Index (OSI) were computed for oxidative stress, and Total Antioxidant Status (TAS) levels were computed for the antioxidant system, for both serum and tissue. Necrosis and microcalcification levels were assessed in the evaluation of testicular histology. P<0.05 was considered statistically significant. AMX-AD group has low necrosis degree than IR, Mean serum and tissue levels of TAS, TOS, and OSI parameters were respectively determined as; for TAS: 0.64±0.11 and 0.96±0.25mmol Trolox Equivalent/L; for TOS: 6.71±0.87 and 9.40±1.03μmolH2O2 equivalent/L; for OSI: 11.94±3.74 and 10.70±4.23 arbitrary unit. Our study has investigated for the first time in the literature the efficacy of amniotic fluid in preventing testicular IR damage, and used amniomax (AMX) for this purpose. The limitation of our study may be the small number of rat in the groups. We think an injection after detorsion is more favorable considering that the AMX-AD group demonstrated significantly lower levels of TOS in serum and tissue and OSI in serum, and significantly higher serum levels of TAS compared to the AMX-BD group, as well as the fact that the morphological protection effect was only observed for injections performed immediately after detorsion.

Quantitative analysis of retinal intermediate and deep capillary plexus in patients with retinal deep vascular complex ischemia.

To quantitatively analyze the retinal intermediate and deep capillary plexus (ICP and DCP) in patients with retinal deep vascular complex ischemia (RDVCI), using 3D projection artifacts removal (3D PAR) optical coherence tomography angiography (OCTA). RDVCI patients and gender- and age-matched healthy controls were assessed and underwent OCTA examinations. The parafoveal vessel density (PFVD) of retinal deep vascular complex (DVC), ICP, and DCP were analyzed, and the percentage of reduction (PR) of PFVD was calculated. Twenty-four eyes in 22 RDVCI patients (20 in acute phase and 4 in chronic phase) and 24 eyes of 22 healthy subjects were enrolled as the control group. Significant reduction of PFVD in DVC, ICP, and DCP was observed in comparison with the controls (DVC: acute: 43.59%±6.58% vs 49.92%±5.49%, PR=12.69%; chronic: 43.50%±3.33% vs 51.20%±3.80%, PR=15.04%. ICP: acute: 40.28%±7.91% vs 46.97%±7.14%, PR=14.23%; chronic: 41.48%±2.87% vs 46.43%±3.29%, PR=10.66%. DCP: acute: 45.44%±8.27% vs 51.51%±9.97%, PR=11.79%; chronic: 37.78%±3.48% vs 51.73%±5.17%, PR=26.97%; all P<0.05). No significant PR difference was found among DVC, ICP, and DCP of RDVCI in acute phase (P=0.812), but significant difference in chronic phase (P=0.006, DVC vs DCP, ICP vs DCP). No significant difference in PR between acute and chronic phases in the DVC (P=0.735) or ICP (P=0.681) was found, but significant difference in the DCP (P=0.041). The PFVD of DVC, ICP, and DCP in RDVCI is significantly decreased in both acute and chronic phases. ICP impairment is stabilized from acute to chronic phase in RDVCI, whereas subsequent DCP impairment is uncovered and can be explained by ischemia-reperfusion damage.

Kidney Transplants in Controlled Donation Following Circulatory Death, or Maastricht Type III Donors, With Abdominal Normothermic Regional Perfusion, Optimizing Functional Outcomes.

Warm ischemia time and ischemia-reperfusion damage result in higher rates of delayed graft function and primary nonfunction in kidney transplants (KTs) from controlled donation after circulatory death (cDCD). This study aimed to assess early and late kidney function and patient and graft survival of KT from cDCD preserved with normothermic regional perfusion (NRP) and to compare with KT from brain death donors (DBDs) and cDCD preserved with rapid recovery (RR). Patients who received a KT at our institution from 2012 to 2018 were included, with a minimum follow-up period of 1 y. They were categorized by donor type and conditioning methods: DBD, cDCD with NRP, and cDCD with RR. Early and late graft function, along with patient and graft survival were analyzed in all groups. A total of 182 KT recipients were included in the study (98 DBD and 84 cDCD). Out of the cDCDs, 24 kidneys were recovered with the use of NRP and 62 with RR; 22 of the 24 kidneys were ultimately transplanted. The cDCD using NRP group showed lower rates of delayed graft function compared with the cDCD with RR group (36.3% versus 46.7%, P = 0.01). Also, primary nonfunction rates were lower in the cDCD using NRP group (4.5% versus 6.4% cDCD-RR and 10.2% DBD). Patient survival rates were >90% in all groups. No differences were found in graft survival rates at 1 y. The use of abdominal NRP improves early function recovery of KT from cDCD, making their outcomes comparable with those of DBD.

PPARγ Plays an Important Role in Acute Hepatic Ischemia-Reperfusion Injury via AMPK/mTOR Pathway.

Background Hepatic ischemia-reperfusion (IR) injury is one of the severe complications associated with liver surgery and leads to liver dysfunction. PPARγ is always linked with various physiologic pathways, and it can alleviate liver damage in IR injury. Aim In this study, we explored the potential mechanism of PPARγ in the pathogenesis of hepatic IR injury by mice model. Methods After treated with si-PPARγ or rosiglitazone, mice were subjected to hepatic ischemia-reperfusion. Liver tissue and blood samples were collected to evaluate liver injury and detected relative mRNA and protein expressions. Results The expression of PPARγ was increased after reperfusion. And the alleviation of PPARγ aggravated the liver damage in IR; at the same time, upregulation of the expression of PPARγ released the liver damage. And these effects of PPARγ in IR were related to the AMPK/mTOR/autophagy signaling pathway. Conclusion PPARγ plays an important role in hepatic IR injury at least partly via the AMPK/mTOR/autophagy pathway.

Nephroprotective Efficacy of Sugammadex in Ischemia-Reperfusion Injury: An Experimental Study in a Rat Model.

Background: It is known that ischemia-reperfusion damage in the kidney is one of the most common causes of acute kidney failure. It is also known that reduced renal damage has a nephroprotective effect by reducing the release of inflammatory and vasoactive peptides that cause tissue damage. Therefore, we think that reperfusion caused by ischemia in kidney damage may be an important focus for clinical research.Methods: A total of 21 healthy 230-250 g female rats were used in our experimental study. During the experiment, animals were randomly divided into three groups, each containing seven rats. Group 1: The group that underwent left nephrectomy with a sham operation. Group 2: Left renal ischemia for 60 minutes, then left nephrectomy followed by 45 minutes of reperfusion. Group 3: Left renal ischemia for 60 minutes, then reperfusion for 45 minutes, followed by left nephrectomy. In this group, sugammadex was given intravenously at a dose of 100 mg/kg at the beginning of reperfusion. In the histomorphological examination, damage findings of tubules atrophy, dilation and cast formation, tubular epithelial brush border loss and vacuolization, presence of fibrosis as interstitial structural change, capillary vasodilatation/congestion and neutrophilic cell infiltrates in interstitial spaces, and morphological changes in glomeruli were evaluated.Results: When evaluated based on tubular brush border, there were no significant differences between Group 2 and Group 1 (P = 0.454), while the damage in Group 3 was less significant than Group 2 (P = 0.017). When evaluated in terms of tubular vacuolization, there was no significant difference between Group 2 and Group 1 (P = 0.902), while the damage in Group 3 was less significant than Group 2 (P = 0.017).Conclusion: We believe that 100 mg/kg sugammadex given at the beginning of reperfusion after one hour of ischemic condition on rats has a histochemically detectable nephroprotective effect.

Characterizing Autophagy in the Cold Ischemic Injury of Small Bowel Grafts: Evidence from Rat Jejunum.

Cold ischemic injury to the intestine during preservation remains an unresolved issue in transplantation medicine. Autophagy, a cytoplasmic protein degradation pathway, is essential for metabolic adaptation to starvation, hypoxia, and ischemia. It has been implicated in the cold ischemia (CI) of other transplantable organs. This study determines the changes in intestinal autophagy evoked by cold storage and explores the effects of autophagy on ischemic grafts. Cold preservation was simulated by placing the small intestines of Wistar rats in an IGL-1 (Institute George Lopez) solution at 4 °C for varying periods (3, 6, 9, and 12 h). The extent of graft preservation injury (mucosal and cellular injury) and changes in autophagy were measured after each CI time. Subsequently, we determined the differences in apoptosis and preservation injury after activating autophagy with rapamycin or inhibiting it with 3-methyladenine. The results revealed that ischemic injury and autophagy were induced by cold storage. Autophagy peaked at 3 h and subsequently declined. After 12 h of storage, autophagic expression was reduced significantly. Additionally, enhanced intestinal autophagy by rapamycin was associated with less tissue, cellular, and apoptotic damage during and after the 12-h long preservation. After reperfusion, grafts with enhanced autophagy still presented with less injury. Inhibiting autophagy exhibited the opposite trend. These findings demonstrate intestinal autophagy changes in cold preservation. Furthermore, enhanced autophagy was protective against cold ischemia–reperfusion damage of the small bowels.

Risk factors for acute kidney injury and mortality in high risk patients undergoing cardiac surgery.

BackgroundAcute Kidney Injury (AKI) represents a clinical condition with poor prognosis. The incidence of AKI in hospitalized patients was about 22–57%. Patients undergoing cardiac surgery (CS) are particularly exposed to AKI because of the related oxidative stress, inflammation and ischemia-reperfusion damage. Hence, the risk profile of patients undergoing CS who develop AKI and who are consequently at increased mortality risk deserves further investigation.MethodsWe designed a retrospective study examining consecutive patients undergoing any type of open-heart surgery from January to December 2018. Patients with a history of AKI were excluded. AKI was diagnosed according to KDIGO criteria. Univariate associations between clinical variables and AKI were tested using logistic regression analysis. Variable thresholds maximizing the association with AKI were measured with the Youden index. Multivariable logistic regression analysis was performed to assess predictors of AKI through backward selection. Mortality risk factors were assessed through the Cox proportional hazard model.ResultsWe studied 158 patients (mean age 51.2±9.7 years) of which 74.7% were males. Types of procedures performed were: isolated coronary artery bypass (CABG, 50.6%), valve (28.5%), aortic (3.2%) and combined (17.7%) surgery. Overall, incidence of AKI was 34.2%. At multivariable analysis, young age (p = 0.016), low blood glucose levels (p = 0.028), estimated Glomerular Filtration Rate (p = 0.007), pH (p = 0.008), type of intervention (p = 0.031), prolonged extracorporeal circulation (ECC, p = 0.028) and cross-clamp (p = 0.021) times were associated with AKI. The threshold for detecting AKI were 91 and 51 minutes for ECC and cross-clamp times, respectively. At survival analysis, the presence of AKI, prolonged ECC and cross-clamp times, and low blood glucose levels forecasted mortality.ConclusionsAKI is common among CS patients and associates with shortened life-expectancy. Several pre-operative and intra-operative predictors are associated with AKI and future mortality. Future studies, aiming at improving prognosis in high-risk patients, by a stricter control of these factors, are awaited.

Cerebroprotective effect of pterostilbene against global cerebral ischemia in rats

Aim of the studyThe role of pterostilbene against induced neurobehavioral alterations in global cerebral ischemia-reperfusion and oxidative damage was studied. Materials and methodsMale SD rats (180–200 g) were exposed for 30 min to bilateral carotid artery occlusion accompanied by 60 min reperfusion to cause cerebral injury. Pretreatment with pterostilbene (200 and 400 mg/kg, orally) was given to the animals for ten days followed by ischemia-reperfusion injury. Various behavioral tests (locomotor activity, neurological score, transfer latency, hanging wire test) were studied. The brain tissues of animals were used for both the biochemical parameters (lipid peroxidation, reduced glutathione, superoxide dismutase, catalase activity) and histopathological study. ResultThe pterostilbene as given orally significantly improved neurobehavioral alterations compared to control ischemia-reperfusion. Treatment with pterostilbene (200, and 400 mg/kg, orally) also significantly attenuated oxidative damage as indicated by reduced lipid peroxidation, nitrite concentration, restored reduced glutathione, and catalase activity as compared to control (ischemia-reperfusion) animals. Overall, pterostilbene treated animals showed non significant histological alteration as compared to ischemia-reperfusion control. ConclusionThis work suggests the beneficial effect of pterostilbene and its therapeutic potential against reperfusion-induced ischemia and associated behavioral changes in rats due to the stabilization of DNA damage with significant free radical scavenging properties.

High dose zoledronic acid increases ischemia-reperfusion damage of the liver.

Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, has been reported to exhibit a protective effect against cancers and prevent bone fractures. It also induces apoptosis by increasing proinflammatory cytokines and oxidative stress. Oxidative stress increases significantly during ischemia-reperfusion (IR) injury. The liver is highly sensitive to IR injury. In this study, we aim to investigate whether high-dose ZA treatment affects the liver during IR. We used twenty-one Sprague-Dawley male rats in our study, and they were subdivided randomly into three groups, each containing seven rats. A single dose of 100 μg/kg ZA was administered via the intraperitoneal route in the ZA group. Forty-eight hours after the ZA administration, infrarenal abdominal aortic cross ligation was performed on the ZA and IR groups. After 2 hours of ischemia, 2 hours of reperfusion was applied. The malondialdehyde (MDA) level of the control group was significantly lower than the IR (p = 0.006) and ZA (p<0.001) groups. However, the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) values of the control group were significantly higher than the values of the IR group (p<0.05, p<0.001, and p<0.05) and ZA group (p = 0.002, p<0.001, and p<0.001). Caspase-3 activity was significantly higher in the IR group as compared to the control group (p<0.001). The caspase-3 activity in the ZA group, on the other hand, was higher than both the control (p<0.001) and IR groups (p<0.001). High-dose ZA may exacerbate liver injury during IR by increasing reactive oxygen species production and apoptosis.

In Situ Observation of mtDNA Damage during Hepatic Ischemia-Reperfusion.

Hepatic ischemia-reperfusion (IR) injury is a severe pathophysiological event during liver surgery or transplantation and could lead to liver failure or even death. The energy supply of mitochondria plays an essential role in preventing IR injury. Mitochondrial DNA (mtDNA) is involved in maintaining the balance of energy by participating in an oxidative phosphorylation process. However, the exact relationship between IR and mtDNA remains unclear by reason of the lack of an accurate real-time analysis method. Herein, we fabricated a mitochondria-targeting fluorescent probe (mtDNA-BP) to explore mtDNA stability and supervise the changes in mtDNA in IR liver. By virtue of pyridinium electropositivity and suitable size, mtDNA-BP could accumulate in mitochondria and insert into the mtDNA groove, which made mtDNA-BP fluoresce strongly. This is attributed to the reduction of the intramolecular rotation energy loss that is restricted by DNA. By in situ fluorescence imaging, we observed in real time that mtDNA damage was aggravated by deteriorating IR injury, so the ROS-mtDNA-mediated IR damage signal pathway was speculated. Furthermore, on the basis of mtDNA-BP real-time response capability for mtDNA, we established a drug-screening method for inhibiting IR injury and found superior therapeutic performance of two potential drugs: pioglitazone and salidroside. This work contributes to our understanding of mtDNA-related disease and provides a new drug analysis method.

Systemic administration of sunflower oil exerts neuroprotection in a mouse model of transient focal cerebral ischaemia.

Natural products are valuable sources of nutraceuticals for the prevention or treatment of ischemic stroke, a major cause of death and severe disability worldwide. Among the mechanisms implicated in cerebral ischemia-reperfusion damage, oxidative stress exerts a pivotal role in disease progression. Given the high antioxidant potential of most components of sunflower oil, we have explored its effects on ischemic brain injury produced in the mouse by transient occlusion of the middle cerebral artery (MCAo). Intraperitoneal (i.p.) administration of sunflower oil at doses of 3 ml/kg (48 h, 24 h and 1 h before MCAo) significantly reduced brain infarct volume and oedema assessed 24 h after the insult. This neuroprotective treatment schedule also prevented the elevation of brain lipid peroxidation produced by MCAo-reperfusion injury. By contrast, doses of 0.03 ml/kg of sunflower oil resulted ineffective on both cerebral damage and lipid peroxidation. Although sunflower oil did not affect serum levels of Diacron-reactive oxygen metabolites (d-ROMs), both 0.03 and 3 ml/kg dosing regimens resulted in the preservation of serum biological antioxidant potential (BAP) that was otherwise dramatically reduced 24 h after MCAo. Sunflower oil represents a promising source of neuroprotective extracts/compounds that can be exploited for the prevention and/or treatment of cerebral ischemia.

CAUSATIVE-INVESTIGATORY RELATIONSHIPS BETWEEN BOWELS MICROBIOTA AND CLINICAL COURSE OF ISCHEMIA-REPERFUSION DAMAGE OF THE BRAIN

The purpose – to carry out the analysis of the current data concerning relationships inthe “bowels microbiota-brain” system at ischemia-reperfusion damages of the brain.Conclusions.1. The analysis of the literature data testify to the views discrepancy, existing today, on therole of the bowels dysbacteriosis (neuroprotective or neurodegenerative) in the clinicalcourse of ischemic damages of the brain.2. Numerous experimental investigations substantiated the bowels microbiota role:homeostasis derangements of T-cells, which have the determined role in the secondaryneuroinflammation following cerebral ischemia; in the ratio change of their subpopulationsTreg-Th17 and migration of the bowels lymphocytes into the ischemic brain.

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

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&lt;0.001), nicotinamide adenine dinucleotide phosphate-oxidase (NOX) (p&lt;0.001), and cytochrome C (Cyt-C) (p&lt;0.001), and increase on antioxidant enzyme catalase (CAT) (p&lt;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&gt; 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.

Answer to the editor “Investigation of the Protective Effect of Nesfatin‐1 on the Tectic Ischemia‐Reperfusion Damage: An Experimental Study”

AndrologiaVolume 53, Issue 3 e13940 LETTER TO THE EDITOR Answer to the editor “Investigation of the Protective Effect of Nesfatin-1 on the Tectic Ischemia-Reperfusion Damage: An Experimental Study” Mehmet Çetinkaya, Corresponding Author Mehmet Çetinkaya [email protected] [email protected] orcid.org/0000-0001-8395-646X Urology Department, Mugla Sitki Kocman University, Mugla, 48000 Turkey Correspondence Mehmet Çetinkaya, Urology Department, Mugla Sitki Kocman University, 48000 Mugla, Turkey. Email: [email protected]Search for more papers by this authorOmer Erdogan, Omer Erdogan orcid.org/0000-0001-8788-8302 Urology Department, Siirt State Hospital, Siirt, TurkeySearch for more papers by this author Mehmet Çetinkaya, Corresponding Author Mehmet Çetinkaya [email protected] [email protected] orcid.org/0000-0001-8395-646X Urology Department, Mugla Sitki Kocman University, Mugla, 48000 Turkey Correspondence Mehmet Çetinkaya, Urology Department, Mugla Sitki Kocman University, 48000 Mugla, Turkey. Email: [email protected]Search for more papers by this authorOmer Erdogan, Omer Erdogan orcid.org/0000-0001-8788-8302 Urology Department, Siirt State Hospital, Siirt, TurkeySearch for more papers by this author First published: 08 March 2021 https://doi.org/10.1111/and.13940Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume53, Issue3April 2021e13940 RelatedInformation

Iron accumulation in skeletal muscles of old mice is associated with impaired regeneration after ischaemia-reperfusion damage.

BackgroundOxidative stress is implicated in the insidious loss of muscle mass and strength that occurs with age. However, few studies have investigated the role of iron, which is elevated during ageing, in age‐related muscle wasting and blunted repair after injury. We hypothesized that iron accumulation leads to membrane lipid peroxidation, muscle wasting, increased susceptibility to injury, and impaired muscle regeneration.MethodsTo examine the role of iron in age‐related muscle atrophy, we compared the skeletal muscles of 3‐month‐old with 22‐ to 24‐month‐old 129SvEv FVBM mice. We assessed iron distribution and total elemental iron using laser ablation inductively coupled plasma mass spectrometry and Perls' stain on skeletal muscle cross‐sections. In addition, old mice underwent ischaemia–reperfusion (IR) injury (90 min ischaemia), and muscle regeneration was assessed 14 days after injury. Immunoblotting was used to determine lipid peroxidation (4HNE) and iron‐related proteins. To determine whether muscle iron content can be altered, old mice were treated with deferiprone (DFP) in the drinking water, and we assessed its effects on muscle regeneration after injury.ResultsWe observed a significant increase in total elemental iron (+43%, P < 0.05) and lipid peroxidation (4HNE: +76%, P < 0.05) in tibialis anterior muscles of old mice. Iron was further increased after injury (adult: +81%, old: +135%, P < 0.05) and associated with increased lipid peroxidation (+41%, P < 0.05). Administration of DFP did not impact iron or measures of lipid peroxidation in skeletal muscle or modulate muscle mass. Increased muscle iron concentration and lipid peroxidation were associated with less efficient regeneration, evident from the smaller fibres in cross‐sections of tibialis anterior muscles (−24%, P < 0.05) and an increased percentage of fibres with centralized nuclei (+4124%, P < 0.05) in muscles of old compared with adult mice. Administration of DFP lowered iron after IR injury (PRE: −32%, P < 0.05 and POST: −41%, P < 0.05), but did not translate to structural improvements.ConclusionsMuscles from old mice have increased iron levels, which are associated with increased lipid peroxidation, increased susceptibility to IR injury, and impaired muscle regeneration. Our results suggest that iron is involved in effective muscle regeneration, highlighting the importance of iron homeostasis in muscle atrophy and muscle repair.

Steatotic Livers Are More Susceptible to Ischemia Reperfusion Damage after Transplantation and Show Increased γδ T Cell Infiltration.

Liver transplantation (LTx) is often the only possible therapy for many end-stage liver diseases, but successful long-term transplant outcomes are limited by multiple factors, including ischemia reperfusion injury (IRI). This situation is aggravated by a shortage of transplantable organs, thus encouraging the use of inferior quality organs. Here, we have investigated early hepatic IRI in a retrospective, exploratory, monocentric case-control study considering organ marginality. We analyzed standard LTx biopsies from 46 patients taken at the end of cold organ preparation and two hours after reperfusion, and we showed that early IRI was present after two hours in 63% of cases. Looking at our data in general, in accordance with Eurotransplant criteria, a marginal transplant was allocated at our institution in about 54% of cases. We found that patients with a marginal-organ LTx showing evidence of IRI had a significantly worse one-year survival rate (51% vs. 75%). As we saw in our study cohort, the marginality of these livers was almost entirely due to steatosis. In contrast, survival rates in patients receiving a non-marginal transplant were not influenced by the presence or absence of IRI. Poorer outcomes in marginal organs prompted us to examine pre- and post-reperfusion biopsies, and it was revealed that transplants with IRI demonstrated significantly greater T cell infiltration. Molecular analyses showed that higher mRNA expression levels of CXCL-1, CD3 and TCRγ locus genes were found in IRI livers. We therefore conclude that the marginality of an organ, namely steatosis, exacerbates early IRI by enhancing effector immune cell infiltration. Preemptive strategies targeting immune pathways could increase the safety of using marginal organs for LTx.