Inhaled Argon Impedes Hepatic Regeneration after Ischemia/Reperfusion Injury in Rats

Organoprotective effects of noble gases are subject of current research. One important field of interest is the effect of noble gases on hepatic regenerative capacity. For the noble gas argon, promising studies demonstrated remarkable experimental effects in neuronal and renal cells. The aim of this study was to investigate the effects of argon on the regenerative capacity of the liver after ischemia/reperfusion injury (IRI). Male, Sprague-Dawley rats underwent hepatic IRI by clamping of the hepatic artery. Expression of hepatoproliferative genes (HGF, IL-1β, IL-6, TNF), cell cycle markers (BrdU, TUNEL, Ki-67), and liver enzymes (ALT, AST, Bilirubin, LDH) were assessed 3, 36, and 96 h after IRI. Expression of IL-1β and IL-6 was significantly higher after argon inhalation after 36 h (IL-1β 5.0 vs. 8.7 fold, p = 0.001; IL-6 9.6 vs. 19.1 fold, p = 0.05). Ki-67 was higher in the control group compared to the argon group after 36 h (214.0 vs. 38.7 positive cells/1000 hepatocytes, p = 0.045). Serum levels of AST and ALT did not differ significantly between groups. Our data indicate that argon inhalation has detrimental effects on liver regeneration after IRI as measured by elevated levels of the proinflammatory cytokines IL-1β and IL-6 after 36 h. In line with these results, Ki-67 is decreased in the argon group, indicating a negative effect on liver regeneration in argon inhalation.

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Glycine Protects the Liver from Reperfusion Injury following Pneumoperitoneum

European Surgical Research ◽

10.1159/000490309 ◽

2018 ◽

Vol 59 (1-2) ◽

pp. 91-99 ◽

Cited By ~ 2

Author(s):

Mohammed Al-Saeedi ◽

Arash Nickkholgh ◽

Daniel Schultze ◽

Christa Flechtenmacher ◽

Markus Zorn ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Control Group ◽

Sprague Dawley ◽

Co2 Pneumoperitoneum ◽

Hepatic Microcirculation ◽

Exact Test ◽

Sprague Dawley Rats ◽

Latex Beads

Background: Experimental pneumoperitoneum induces ischemia/reperfusion injury (IRI) in the liver, most likely via Kupffer cell (KC)-dependent mechanisms. Glycine has been shown to ameliorate IRI in various animal models. Thus, this study was performed to assess the effects of glycine on the liver after pneumoperitoneum. Materials and Methods: Sprague-Dawley rats (220–250 g in weight) underwent CO2 pneumoperitoneum (12 mm Hg) for 90 min. Some rats received i.v. glycine (1.5 mL, 300 mM) 10 min before pneumoperitoneum. Controls were given the same volume of Ringer’s solution. Transaminases, hepatic microcirculation, and phagocytosis of latex beads indexing both liver injury and KC activation were examined following pneumoperitoneum. Analysis of variance (ANOVA), plus a subsequent t test or χ2 test (or Fisher’s exact test) were carried out as appropriate. Results are presented as mean ± SEM. Results: Glycine significantly decreased lactate dehydrogenase at 1 h and both aspartate aminotransferase and alanine aminotransferase at 2 h after pneumoperitoneum from 477 ± 43, 154 ± 17, and 60 ± 6 U/L in controls to 348 ± 25, 101 ± 11, and 34 ± 3 U/L, respectively (p < 0.05). In parallel, glycine significantly decreased both the rate of permanent adherence of leukocytes to the endothelium by up to 35% and the rate of phagocytosis by > 50% compared to the control group. Conclusion: Glycine decreased IRI after pneumoperitoneum, most likely via KC-dependent mechanisms.

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Melatonin and Glycine Reduce Uterus Ischemia/Reperfusion Injury in a Rat Model of Warm Ischemia

International Journal of Molecular Sciences ◽

10.3390/ijms22168373 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8373

Author(s):

Viktorija Zitkute ◽

Mindaugas Kvietkauskas ◽

Vygante Maskoliunaite ◽

Bettina Leber ◽

Diana Ramasauskaite ◽

...

Keyword(s):

Reperfusion Injury ◽

Rat Model ◽

Ischemia Reperfusion Injury ◽

Cell Damage ◽

Ischemia Reperfusion ◽

Combined Treatment ◽

Warm Ischemia ◽

Control Group ◽

Protective Effects ◽

Sprague Dawley

Ischemia/reperfusion injury (IRI) remains a significant problem to be solved in uterus transplantation (UTx). Melatonin and glycine have been shown to possess direct cytoprotective activities, mainly due to their antioxidative and anti-inflammatory properties. The aim of this study was to investigate the protective effects of melatonin and glycine and their combination on IRI in a rat model of warm ischemia. In this study, Sprague-Dawley rats were assigned to eight groups, including sham and IRI (n = 80). Melatonin and glycine alone or their combination were administered prior to 1 h of uterus ischemia followed by 1 h of reperfusion. Melatonin (50 mg/kg) was administered via gavage 2 h before IRI and glycine in an enriched diet for 5 days prior to intervention. Uterus IRI was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. Histology revealed that uterus IRI was significantly attenuated by pretreatment with melatonin (p = 0.019) and glycine (p = 0.044) alone as well as their combination (p = 0.003). Uterus IRI led to increased myeloperoxidase expression, which was significantly reduced by melatonin (p = 0.004), glycine (p < 0.001) or their combination (p < 0.001). The decline in superoxide dismutase activity was significantly reduced in the melatonin (p = 0.027), glycine (p = 0.038) and combined treatment groups (p = 0.015) when compared to the IRI control group. In conclusion, melatonin, glycine and their combination significantly reduced oxidative stress-induced cell damage after IRI in a small animal warm ischemia model, and, therefore, clinical studies are required to evaluate the protective effects of these well-characterized substances in uterus IRI.

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Gut lymph purification regulates monocyte activity in rats with ischemia-reperfusion injury-induced sepsis

10.1101/2020.02.02.930610 ◽

2020 ◽

Author(s):

Wei Zhang ◽

Jie Chen ◽

Can Jin ◽

Shuncheng Zhang ◽

Juan Gu ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Control Group ◽

Main Process ◽

Toxic Substances ◽

Sprague Dawley ◽

Mhc Molecules ◽

Positive Expression ◽

Expression Rate

ABSTRACTObjectiveTo confirm that gut lymph purification (GLP) based on oXiris regulates monocyte activity by targeting the removal of ischemia-reperfusion injury (IRI)-induced intestinal toxic substances (ITSs) in rats.MethodsSepsis was induced by intestinal IRI in 24 adult male Sprague-Dawley rats that were randomly divided into the control, intestinal IRI, and IRI+GLP groups. The gut lymph fluid (GLF) was drained for 180 minutes. The ITSs levels and the proliferation, apoptosis and positive expression rates of MHC-II molecules of monocytes coincubated with the GLF were detected.ResultsEndotoxin, TNF-α, IL-4, IL-6 and IL-10 levels in the lymph and plasma of the IRI group were significantly higher than those of the control group (p < 0.01). Compared with the IRI group, GLP treatment significantly decreased the ITS levels (p < 0.05). Monocyte proliferation and the positive expression rate of MHC-□ molecules were significantly reduced after co-culturing with GLF upon IRI (p < 0.01), and the apoptotic rate was significantly increased (p < 0.01). However, culturing monocytes with GLP significantly enhanced the monocyte proliferation, increased the positive expression rate of MHC-□ monocytes (p < 0.01), and reduced the apoptotic rate (p < 0.01).ConclusionsGLP therapy based on oXiris effectively removed ITSs from the GLF after IRI, thereby blocking the main process of multiple organ dysfunction syndrome by regulating monocyte activity.

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Favorable Effects of Astaxanthin on Brain Damage due to Ischemia- Reperfusion Injury

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200219121600 ◽

2020 ◽

Vol 23 (3) ◽

pp. 214-224 ◽

Cited By ~ 1

Author(s):

Esra Cakir ◽

Ufuk Cakir ◽

Cuneyt Tayman ◽

Tugba Taskin Turkmenoglu ◽

Ataman Gonel ◽

...

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Brain Damage ◽

Neurological Deficit ◽

Cell Apoptosis ◽

Ischemia Reperfusion Injury ◽

Degradation Products ◽

Ischemia Reperfusion ◽

Control Group ◽

Cortex Cell

Background: Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect. Objective: The aim of this study was to investigate the role of ASX on brain IRI. Methods: A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated. Results: In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05). Conclusion: Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury.

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Abstract 193: Antithrombin Perfluorocarbon Nanoparticles Ameliorate Renal Injury Following Transient Warm Ischemia

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.34.suppl_1.193 ◽

2014 ◽

Vol 34 (suppl_1) ◽

Author(s):

Chandu Vemuri ◽

Junjie Chen ◽

Rohun U Palekar ◽

John S Allen ◽

Xiaoxia Yang ◽

...

Keyword(s):

Reperfusion Injury ◽

Renal Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Warm Ischemia ◽

P Value ◽

Sprague Dawley ◽

Histologic Analysis ◽

Microvascular Thrombosis

Objective: Thrombin mediated microvascular thrombosis plays a crucial role in the pathogenesis of acute renal reperfusion injury following transient ischemia. We hypothesize that anti-thrombin nanoparticles will ameliorate acute renal injury by inhibiting microvascular thrombosis. Methods: Adult, male Sprague Dawley rats were randomized into two groups of 5 to receive tail vein injections of saline or nanoparticles loaded with Phe[D]-Pro-Arg-Chloromethylketone (NP-PPACK). Immediately following injection, all animals underwent operative bilateral renal artery occlusion to create 45 minutes of warm ischemia, followed by restoration of renal blood flow. Blood samples were drawn daily and animals were euthanized on day 1 or 7 for histologic analysis of kidney injury (H&E, TUNEL and thrombin staining). Results: Histologic analysis of renal tissue revealed significant apoptosis, necrosis and thrombin accumulation 1 day after ischemia-reperfusion, confirming acute kidney injury. The peak creatinine (mg/dl) on day 1 was significantly lower in NP-PPACK treated animals (0.57 +/- 0.07 (SEM)) than in saline treated controls (1.40 +/- 0.20 (SEM); p-value <0.01). Furthermore, animals treated with NP-PPACK continued to exhibit less renal dysfunction for 7 days after injury (Figure 1). Conclusion: Histologically confirmed intrarenal thrombosis was detected one day after ischemia-reperfusion injury. Targeted inhibition of thrombin with NP-PPACK prevented a decline in renal function following transient occlusion. Future work will focus on defining the underlying mechanisms of this effect.

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The protective effect of L-arginine, tadalafil, and their combination in rat testes after ischemia and reperfusion injury

Canadian Urological Association Journal ◽

10.5489/cuaj.3872 ◽

2017 ◽

Vol 11 (1-2) ◽

pp. 19 ◽

Cited By ~ 8

Author(s):

Gokhun Ozmerdiven ◽

Burhan Coskun ◽

Onur Kaygisiz ◽

Berna Aytac Vuruskan ◽

Burak Asiltas ◽

...

Keyword(s):

Protective Effect ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Combination Group ◽

Control Group ◽

Ischemia And Reperfusion ◽

Contralateral Testis ◽

Treatment Groups ◽

Testis Torsion

Introduction: Nitric oxide (NO) plays an important role in the ischemia and reperfusion process. In this study, we aimed to examine the effect of L-arginine, tadalafil, and their combination for preventionof the ischemia reperfusion injury after testis torsion in rats.Methods: A total of 40 adult, male Sprague-Dawley rats were allocated into five groups. Three hours of left testicular torsion was performed in each group, excluding the control group. While the ischemia reperfusion (I/R) group had no treatment, I/R + Arg group received L-arginine, I/R + Td group received tadalafil and I/R + Arg + Td group received tadalafil and L-arginine 30 minutes before the detorsion. Then the left testis was untwisted for four hours of reperfusion. After bilateral orchiectomy, lipid peroxidation (LPx) and glutathione (GSH) activities were examined in testicular tissue.Spermatogenesis was evaluated with Johnsen’s score.Results: LPx levels of the I/R group were found to be significantly higher than for groups that received drugs for both testes (p<0.001). GSH levels of the combination group were higher than I/R group inipsilateral testis (p<0.01) and it was significantly higher than other groups for contralateral testis (p<0.001 for I/R group, p<0.01 for I/R + Arg, p<0.05 for I/R + Td). Mean Johnsen’s score of the I/Rgroup was found to be significantly lower than treatment groups in ipsilateral testis (p<0.001 for I/R + Arg + Td group, p<0.01 for other treatment goups) and contralateral testis (p<0.001). The meanJohnsen score of the combination group was significantly higher than that of other treatment groups in ipsilateral testis (p<0.05) and it was significantly higher than in the I/R + Td group in the contralateral testis (p<0.05).Conclusions: L-arginine, tadalafil, and combination of these two molecules showed protective effect against ischemia/reperfusion injury for both testes after unilateral testis torsion.

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Antioxidative and anti-inflammatory impact of valsartan against renal ischemia-reperfusion injury; role of nitric oxide signaling pathway

Immunopathologia Persa ◽

10.15171/ipp.2019.19 ◽

2019 ◽

Vol 5 (2) ◽

pp. e19-e19

Author(s):

Leila Mohmoodnia ◽

Sarina Safari Ahmadvand ◽

Sahar Koushki ◽

Behrooz Farzan ◽

Sajad Papi ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Serum Levels ◽

Renal Ischemia ◽

Control Group ◽

Type I ◽

Angiotensin Receptor ◽

Renal Ischemia Reperfusion Injury ◽

Control Group Group

Introduction: Renal ischemia reperfusion injury is one of the main causes of acute renal failure, which is associated with high mortality. Tissue damage caused by ischemia-reperfusion occurs due to the release of oxygen free radicals. Type I angiotensin receptor antagonists such as valsartan can be useful in the treatment of chronic kidney disease and hypertension. Objectives: We aimed to evaluate the protective effect of valsartan against renal ischemia reperfusion via antioxidant property and nitric oxide (NO) signaling pathway. Materials and Methods: Fifty male Wistar rats (220±10 g) were randomly divided into five groups as follows: Group 1; healthy rats without ischemia-reperfusion (control group). Group 2; rats with ischemia reperfusion (IR) (IR control group). Group 3; rats with IR which received 30 mg/kg valsartan orally. Group 4; rats with IR which received 30 mg/kg valsartan together with 40 mg/kg L-NAME. Group 5; rats with IR which received 30 mg/kg valsartan together with 40 mg/kg L-arginine. To induce ischemia-reperfusion, rats were anesthetized with thiopental and underwent surgery. Then, we induced ischemia with blocking blood vessels for 45 minutes by clamping. Biochemical parameters including urea and creatinine were measured using commercial kits. Oxidative stress and inflammatory parameters were measured by ELISA method. Renal tissues were stained with hematoxylin and eosin. Finally, the Kolmogorov-Smirnov test was used to determine the normal distribution of data. Results: The findings of this study indicated that treatment with valsartan and valsartan plus L-arginine leads to significant decrease in the serum levels of creatinine, urea, and albumin/creatinine, malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in contrast to IR control group which has increased level of these parameters. On the other hand, treatment with valsartan and valsartan plus L-arginine lead to increase in the serum levels of glutathione peroxidase (GPX), in contrast to ischemia reperfusion control group. Conclusion: Our data revealed that valsartan as a type I angiotensin receptor antagonist could decrease oxidative stress and inflammation due to renal ischemia reperfusion injury. Hence, valsartan could propose as a therapeutic agent for kidney diseases such as renal ischemia-reperfusion injury regarded to these renoprotective effects.

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Dexmedetomidine Attenuates Lung Ischemia-reperfusion Injury in Rats by Reducing Mitochondrial Dysfunction

10.21203/rs.3.rs-120188/v1 ◽

2020 ◽

Author(s):

Yan Zhang ◽

Yao Lu ◽

Kai Wang ◽

Mei-yan Zhou ◽

Cong-you Wu ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Reperfusion Injury ◽

Mitochondrial Biogenesis ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Weight Ratio ◽

Oxygenation Index ◽

Lung Damage ◽

Peroxisome Proliferator ◽

Sprague Dawley

Abstract Background: Lung ischemia-reperfusion injury (LIRI) is a significant clinical problem occurring after lung transplantation. LIRI is mediated by the overproduction of reactive oxygen species (ROS) and inflammatory activation. Previous studies have confirmed that dexmedetomidine (DEX) exerts a protective effect on LIRI, which potentially causes severe mitochondrial dysfunction. However, the specific mechanisms remain unclear. Our study was to explore whether dexmedetomidine exerts a beneficial effect on LIRI by reducing mitochondrial dysfunction. Methods: Two different models were used in our study. For the in vivo experiment, thirty-two male Sprague-Dawley rats were randomly divided into Sham, ischemia-reperfusion (I/R), DEX+I/R and DEX+yohimbine+I/R (DY+I/R) groups. Similarly, pulmonary vascular endothelial cells (PVECs) from SD rats were divided into Control, oxygen glucose deprivation (OGD), D+OGD and DY+OGD groups.Results: In our experiment, we confirmed severe lung damage after LIRI that was characterized by significantly pulmonary histopathology injury, a decrease in the oxygenation index (PaO2/FiO2) and an increase in the wet-to-dry weight ratio, while DEX treatment mitigated this damage. In addition, the DEX pretreatment significantly attenuated I/R-induced oxidative stress by decreasing the level of ROS in the mitochondria in vitro. Moreover, the DEX treatment enhanced mitochondrial biogenesis and autophagy by increasing the expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), mitochondrial transcription factor A (Tfam), PTEN-induced putative kinase 1 (PINK1), Parkin and dynamin 1-like protein 1 (Drp1). Conclusions: These data suggest that DEX may alleviate LIRI by reducing mitochondrial dysfunction through the induction of mitochondrial biogenesis and autophagy.

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Inhibiting mTOR enhanced Cardiac STAT3 Phosphorylation at Site Ser 727 and Attenuated Myocardial Ischemia Reperfusion Injury in Diabetic Rats

10.21203/rs.3.rs-266485/v1 ◽

2021 ◽

Author(s):

Xiang Xie ◽

Zhongbao Zhao ◽

Danyong Liu ◽

Dengwen Zhang ◽

Yi He ◽

...

Keyword(s):

Reperfusion Injury ◽

Mtor Inhibitor ◽

Troponin I ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Diabetic Rats ◽

H9c2 Cells ◽

Sprague Dawley ◽

Mtor Inhibition ◽

Stat3 Phosphorylation

Abstract Background Reduced levels of myocardial STAT3 activity in diabetic hearts may contribute to the increased susceptibility to ischemia-reperfusion injury (I/RI). The protein mammalian target of rapamycin (mTOR) can regulate metabolism and cell processes and plays major roles in the dynamics of I/RI. However, the role of mTOR in regulation of myocardial STAT3 and thereby affect myocardial I/RI in diabetes at relatively late stages of the disease is unknown. Methods Diabetes was induced by Streptozotocin in Sprague-Dawley rats. Myocardial I/RI was achieved with coronary occlusion for 30 minutes and reperfusion for 2 hours in absence or presence of the mTOR inhibitor rapamycin. In vitro cardiomyocyte hypoxia/re-oxygenation (H/R) was established within H9C2 cells. Results In diabetic rats, the levels of troponin-I (Tn-I), lipid peroxidation products 15-F2t-Isoprostane (15-F2t-Iso) and MDA, and the expression of protein mTOR were all significantly increased,and SOD releasing, the expression of protein phosphorylation of STAT3(p-STAT3-Ser727) were both significantly decreased compared to non-diabetic rats. Myocardial I/RI significantly increased the infract size (IS) and further increased the mTOR activation and decreased p-STAT3-Ser727 compared to diabetic rats. The selective mTOR inhibitor rapamycin reversed these changes and conferred cardioprotective effect. In H9C2 cells, high glucose (HG) significantly increased lactic dehydrogenase (LDH) release, apoptosis cells, ROS release, activation of mTOR, and decreased p-STAT3-Ser727. H/R further increased cellular injury, mTOR knock-down significantly reduced H/R injury. Conclusion Myocardial mTOR was enhanced in diabetes and contributed to I/RI. mTOR inhibition attenuated myocardial I/RI through increasing p-STAT3-Ser727.

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Effects of Thyroid Hormone Analogue and a Leukotrienes Pathway-Blocker on Reperfusion Injury Attenuation after Heart Transplantation

ISRN Pharmacology ◽

10.1155/2013/303717 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8

Author(s):

Fadhil G. Al-Amran ◽

Najah R. Hadi ◽

Haider S. H. Al-Qassam

Keyword(s):

Myocardial Ischemia ◽

Heart Transplantation ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Treated Group ◽

Control Group ◽

Group I ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

Background. Global myocardial ischemia reperfusion injury after heart transplantation is believed to impair graft function and aggravate both acute and chronic rejection episodes. Objectives. To assess the possible protective potential of MK-886 and 3,5-diiodothyropropionic acid DITPA against global myocardial ischemia reperfusion injury after heart transplantation. Materials and Methods. Adult albino rats were randomized into 6 groups as follows: group I sham group; group II, control group; groups III and IV, control vehicles (1,2); group V, MK-886 treated group. Donor rats received MK-886 30 min before transplantation, and the same dose was repeated for recipients upon reperfusion; in group VI, DITPA treated group, donors and recipients rats were pretreated with DITPA for 7 days before transplantation. Results. Both MK-886 and DITPA significantly counteract the increase in the levels of cardiac TNF-α, IL-1β, and ICAM-1 and plasma level of cTnI (). Morphologic analysis showed that both MK-886 and DITPA markedly improved () the severity of cardiac injury in the heterotopically transplanted rats. Conclusions. The results of our study reveal that both MK-886 and DITPA may ameliorate global myocardial ischemia reperfusion injury after heart transplantation via interfering with inflammatory pathway.

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