scholarly journals Custodiol-N Is Superior to Custodiol® Solution in Experimental Rat Uterus Preservation

2020 ◽  
Vol 21 (21) ◽  
pp. 8015
Author(s):  
Viktorija Zitkute ◽  
Mindaugas Kvietkauskas ◽  
Vygante Maskoliunaite ◽  
Bettina Leber ◽  
Diana Ramasauskaite ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Injury ◽  
Protective Role ◽  
Sprague Dawley ◽  
Cold Ischemia ◽  
Tissue Samples ◽  
Cold Preservation ◽  
Uterus Transplantation ◽  
Tissue Edema

Uterus transplantation (UTx) is the first and only available treatment for women with absolute uterine factor infertility. However, clinical application is limited by the lack of organs, ischemia/reperfusion injury, as well as immunosuppression after UTx. Several different preservation solutions are used in experimental and clinical UTx, including Custodiol® solution. Recently, the novel Custodiol-N solution was developed with superior results in organ preservation. However, the solution was not tested yet in UTx. Therefore, the aims of this study were to evaluate the effect of Custodiol-N in uterus prolonged cold preservation time (8 and 24 h), compared to Custodiol® solution. Uterus tissue samples were obtained from adult Sprague Dawley rats (n = 10/group). Cold ischemic injury was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. After 8 h of cold ischemia, higher percentage of tissue edema, necrosis signs and myeloperoxidase expression, as well as lower superoxide dismutase activity were found in Custodiol® compared to Custodiol-N (p < 0.05). These differences were more pronounced after 24 h of cold preservation time (p < 0.05). This study demonstrated that Custodiol-N protects uterus grafts from cold ischemic injury better than standard Custodiol® most likely via inhibition of oxidative stress and tissue edema. It seems that iron chelators in the composition of Custodiol-N play an important protective role against cold ischemia.

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

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 396
Author(s):  
Ibitamuno Caleb ◽  
Luca Erlitz ◽  
Vivien Telek ◽  
Mónika Vecsernyés ◽  
György Sétáló ◽  
...  
Keyword(s):  
Cold Storage ◽  
Ischemia Reperfusion ◽  
Ischemic Injury ◽  
Degradation Pathway ◽  
Metabolic Adaptation ◽  
Cold Ischemia ◽  
Cold Preservation ◽  
Opposite Trend ◽  
Preservation Injury ◽  
Apoptotic Damage

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.

scholarly journals FTY720 Effects on Inflammation and Liver Damage in a Rat Model of Renal Ischemia-Reperfusion Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Anthony D. Foster ◽  
Diego Vicente ◽  
Nicholas Clark ◽  
Crystal Leonhardt ◽  
Eric A. Elster ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Treatment Strategies ◽  
Serum Markers ◽  
Organ Injury ◽  
Gene Transcript ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
The Impact

Objective. Ischemia-reperfusion injury (IRI) produces systemic inflammation with the potential for causing organ failure in tissues peripheral to the initial site of injury. We speculate that treatment strategies that dampen inflammation may be therapeutically beneficial to either the initial site of injury or peripheral organs. To test this, we evaluated the impact of FTY720-induced sequestration of circulating mature lymphocytes on renal IRI and secondary organ injury. Methods. A microvascular clamp was surgically placed around the left renal pedicle of anesthetized male Sprague-Dawley rats with either vehicle or FTY720 treatment (0.3 mg/kg) intravenously injected after 15 min of ischemia. Blood flow was restored after 60 min. Cohorts of anesthetized rats were euthanized at 6, 24, or 72 hrs with tissue samples collected for analysis. Results. FTY720 treatment resulted in profound T lymphocyte reduction in peripheral blood. Histopathologic examination, clinical chemistries, and gene transcript expression measurements revealed that FTY720 treatment reduced hepatocellular degeneration, reduced serum markers of liver injury (ALT/AST), and reduced the expression of gene targets associated with IRI. Conclusion. These findings support an anti-inflammatory effect of FTY720 in the liver where the expression of genes associated with apoptosis, chemotaxis, and the AP-1 transcription factor was reduced. Findings presented here provide the basis for future studies evaluating FTY720 as a potential therapeutic agent to treat complications resulting from renal IRI.

Nitric Oxide Modulation as a Potential Molecular Mechanism Underlying the Protective Role of NaHS in Liver Ischemia Reperfusion Injury

2021 ◽  
Vol 14 ◽  
Author(s):  
Salwa A. Ibrahim ◽  
Seham A. Abdel-Gaber ◽  
Mohamed A. Ibrahim ◽  
Entesar F. Amin ◽  
Rehab K. Mohammed ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Histopathological Examination ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Albino Rats ◽  
High Morbidity ◽  
Tissue Samples ◽  
Sodium Hydrosulfide ◽  
Tnf Α

Background and aim: Liver IR is a frequent clinical complication with high morbidity and mortality. The present study evaluated the possible protective effect of sodium hydrosulfide (NaHS), a H2S donor, in IR-induced hepatic injury and explored the mechanisms of actions of the investigated drug. Methods: Male albino rats (200-230 g) were divided into the following groups: group 1:Sham-operated non treated rats, group 2: IR non treated rats, group 3: L-NNA + IR rats, group 4: NaHS + IR rats, group 5: L-NNA + NaHS + IR rats. Blood samples were collected for ALT determination. Liver tissue samples were used for the assessment of GPx, catalase, SOD, MDA, total nitrites and TNF-α. Parts from the liver were fixed in 10% formalin solution for histopathological examination and immunohistochemical examination of iNOS, eNOS and caspase-3. Results: NaHS protected the liver against IR. This hepatoprotection was associated with normalization of antioxidant enzyme activity and decrease in hepatic MDA, TNF-α and expression of caspase-3 and iNOS. Conclusion: NaHS is hepatoprotective in IR injury. The hepatoprotective effects of NaHS are associated with antioxidant, anti-inflammatory and antiapoptotic effects. These effects are probably mediated via NO modulation.

scholarly journals Aldehyde Dehydrogenase 2 (ALDH2) in Rat Fatty Liver Cold Ischemia Injury

2018 ◽  
Vol 19 (9) ◽  
pp. 2479 ◽  
Author(s):  
Arnau Panisello-Roselló ◽  
Norma Alva ◽  
Marta Flores ◽  
Alexandre Lopez ◽  
Carlos Castro Benítez ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Reperfusion Injury ◽  
Aldehyde Dehydrogenase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Related Factor ◽  
Aldehyde Dehydrogenase 2 ◽  
Cold Ischemia ◽  
Liver Preservation

Institut George Lopez-1 (IGL-1) and Histidine-tryptophan-ketoglutarate (HTK) solutions are proposed as alternatives to UW (gold standard) in liver preservation. Their composition differs in terms of the presence/absence of oncotic agents such as HES or PEG, and is decisive for graft conservation before transplantation. This is especially so when fatty (steatotic) livers are used since these grafts are more vulnerable to ischemia insult during conservation. Their composition determines the extent of the subsequent reperfusion injury after transplantation. Aldehyde dehydrogenase-2 (ALDH2), a mitochondrial enzyme, has been reported to play a protective role in warm ischemia-reperfusion injury (IRI), but its potential in fatty liver cold ischemic injury has not yet been investigated. We evaluated the relevance of ALDH2 activity in cold ischemia injury when fatty liver grafts from Zucker Obese rats were preserved in UW, HTK, and IGL-1 solutions, in order to study the mechanisms involved. ALDH2 upregulation was highest in livers preserved in IGL-1. It was accompanied by a decrease in transaminases, apoptosis (Caspase 3 and TUNEL assay), and lipoperoxidation, which was concomitant with the effective clearance of toxic aldehydes such as 4-hydroxy-nonenal. Variations in ATP levels were also determined. The results were consistent with levels of NF-E2 p45-related factor 2 (Nrf2), an antioxidant factor. Here we report for the first time the relevance of mitochondrial ALDH2 in fatty liver cold preservation and suggest that ALDH2 could be considered a potential therapeutic target or regulator in clinical transplantation.

Protective role of NF-κB in liver cold ischemia/reperfusion injury: effects of IκB gene therapy

2001 ◽  
Vol 33 (1-2) ◽  
pp. 602 ◽  
Author(s):  
Y Takahashi ◽  
R.W Ganster ◽  
T Ishikawa ◽  
T Okuda ◽  
A Gambotto ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Cold Ischemia

scholarly journals Donor Preconditioning with Inhaled Sevoflurane Mitigates the Effects of Ischemia-Reperfusion Injury in a Swine Model of Lung Transplantation

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Alessandro Bertani ◽  
Vitale Miceli ◽  
Lavinia De Monte ◽  
Giovanna Occhipinti ◽  
Valeria Pagano ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Lung Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Lung ◽  
Outcome Analysis ◽  
Swine Model ◽  
Cold Ischemia ◽  
Tissue Samples

Primary graft dysfunction (PGD) and ischemia-reperfusion injury (IRI) occur in up to 30% of patients undergoing lung transplantation and may impact on the clinical outcome. Several strategies for the prevention and treatment of PGD have been proposed, but with limited use in clinical practice. In this study, we investigate the potential application of sevoflurane (SEV) preconditioning to mitigate IRI after lung transplantation. The study included two groups of swines (preconditioned and not preconditioned with SEV) undergoing left lung transplantation after 24-hour of cold ischemia. Recipients’ data was collected for 6 hours after reperfusion. Outcome analysis included assessment of ventilatory, hemodynamic, and hemogasanalytic parameters, evaluation of cellularity and cytokines in BAL samples, and histological analysis of tissue samples. Hemogasanalytic, hemodynamic, and respiratory parameters were significantly favorable, and the histological score showed less inflammatory and fibrotic injury in animals receiving SEV treatment. BAL cellular and cytokine profiling showed an anti-inflammatory pattern in animals receiving SEV compared to controls. In a swine model of lung transplantation after prolonged cold ischemia, SEV showed to mitigate the adverse effects of ischemia/reperfusion and to improve animal survival. Given the low cost and easy applicability, the administration of SEV in lung donors may be more extensively explored in clinical practice.

PROTECTIVE ROLE OF NFκB IN LIVER COLD ISCHEMIA/ REPERFUSION INJURY.

2000 ◽  
Vol 69 (Supplement) ◽  
pp. S376
Author(s):  
Yoshihito Takahashi ◽  
Raymond W. Ganster ◽  
Takashi Ishikawa ◽  
Toyokazu Okuda ◽  
Andrea Gambotto ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Cold Ischemia

Human breast milk suppresses the transcriptional regulation of IL-1β-induced NF-κB signaling in human intestinal cells

2004 ◽  
Vol 287 (5) ◽  
pp. C1404-C1411 ◽  
Author(s):  
Ryoko Minekawa ◽  
Takashi Takeda ◽  
Masahiro Sakata ◽  
Masami Hayashi ◽  
Aki Isobe ◽  
...  
Keyword(s):  
Breast Milk ◽  
Pathogenic Bacteria ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nuclear Factor Κb ◽  
Protective Role ◽  
Intestinal Cells ◽  
Human Breast Milk ◽  
Human Breast ◽  
Activation Pathway

Neonatal necrotizing enterocolitis (NEC), which is a disease with a poor prognosis, is considered to be caused by the coincidence of intestinal ischemia-reperfusion injury and systemic inflammation due to the colonization of pathogenic bacteria. Interleukin (IL)-8, a proinflammatory cytokine, plays an important role in the pathophysiology of NEC. It was recently reported that IL-1β activates the IL-8 gene by regulating the transcriptional nuclear factor κB (NF-κB) signaling pathways in intestinal cells. The protective role of maternal milk in NEC pathogenesis has been reported in both human and animal studies. In this study, we show that human breast milk dramatically suppressed the IL-1β-induced activation of the IL-8 gene promoter by inhibiting the activation pathway of NF-κB. Moreover, we also show that human breast milk induced the production of IκBα. These results suggest that human breast milk could be protective and therapeutic in neonates with NEC by inhibiting the activation pathway of NF-κB.

Interleukin 35 protects cardiomyocytes following ischemia/reperfusion-induced apoptosis via activation of mitochondrial STAT3

2021 ◽  
Author(s):  
Fengyun Zhou ◽  
Ting Feng ◽  
Xiangqi Lu ◽  
Huicheng Wang ◽  
Yangping Chen ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Cytochrome C Release ◽  
Neonatal Cardiomyocytes ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Abstract Mitochondrial reactive oxygen species (mtROS)-induced apoptosis has been suggested to contribute to myocardial ischemia/reperfusion injury. Interleukin 35 (IL-35), a novel anti-inflammatory cytokine, has been shown to protect the myocardium and inhibit mtROS production. However, its effect on cardiomyocytes upon exposure to hypoxia/reoxygenation (H/R) damage has not yet been elucidated. The present study aimed to investigate the potential protective role and underlying mechanisms of IL-35 in H/R-induced mouse neonatal cardiomyocyte injury. Mouse neonatal cardiomyocytes were challenged to H/R in the presence of IL-35, and we found that IL-35 dose dependently promotes cell viability, diminishes mtROS, maintains mitochondrial membrane potential, and decreases the number of apoptotic cardiomyocytes. Meanwhile, IL-35 remarkably activates mitochondrial STAT3 (mitoSTAT3) signaling, inhibits cytochrome c release, and reduces apoptosis signaling. Furthermore, co-treatment of the cardiomyocytes with the STAT3 inhibitor AG490 abrogates the IL-35-induced cardioprotective effects. Our study identified the protective role of IL-35 in cardiomyocytes following H/R damage and revealed that IL-35 protects cardiomyocytes against mtROS-induced apoptosis through the mitoSTAT3 signaling pathway during H/R.

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