scholarly journals Intraperitoneal Mesalamine Does Not Restores Mesenteric Perfusion or Prevent Mucosal Injury Following Intestinal Ischemia and Reperfusion

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Thomas Knowles ◽  
Brian Hosfield ◽  
Chris Shelley ◽  
Troy Markel
Keyword(s):  
Intestinal Ischemia ◽  
Cell Damage ◽  
Acute Mesenteric Ischemia ◽  
Mucosal Injury ◽  
Laser Doppler ◽  
Cellular Damage ◽  
Midline Laparotomy ◽  
Intestinal Necrosis ◽  
Mesenteric Perfusion ◽  
Sudden Decrease

Background and Hypothesis: Acute Mesenteric Ischemia (AMI) is characterized by a sudden decrease in blood flow to varying segments of the small intestine. It can lead to cellular damage, life-threatening intestinal necrosis and, if corrected, subsequent reperfusion injury. Reducing inflammation is key to preventing further cell damage. We therefore hypothesized that administration of mesalamine prior to intestinal ischemia would reduce epithelial cell damage by I/R and restore mesenteric perfusion. Project Methods: C57Bl6J wild type (WT) mice were assigned to mesalamine or vehicle treatment groups (N=8/group). Prior to surgery, mice underwent intraperitoneal injection of treatment. Midline laparotomy was performed. Intestines were eviscerated, superior mesenteric artery (SMA) located, and baseline intestinal perfusion determined using Laser Doppler. SMA was then occluded to induce intestinal ischemia for sixty minutes, thereafter the occlusion was removed. Mesenteric reperfusion was then determined by Laser Doppler. Midline incisions were reapproximated with suture and animals were allowed to recover. After twentyfour hours, animals were re-anesthetized and underwent final assessment of mesenteric perfusion by Laser-Doppler. Animals were then euthanized, and intestines explanted. A portion of tissue was snap frozen for assessment for proinflammatory cytokines by ELISA. Another portion of tissue was stained with H&E and scored for intestinal mucosal injury. Data were assessed for normalcy and compared by Mann-Whitney-U test. P<.05 was significant. Results: Preliminary data suggests mesalamine treated mice show no significant change in mortality compared to vehicle. Mesalamine treated mice also show an insignificant increase in histological damage score. Despite this, they show an insignificant improvement in oxygen perfusion. Conclusion: Intraperitoneal mesalamine administration does not appear to be a useful method for limiting cell damage in GI diseases associated with AMI such as necrotizing enterocolitis. A larger sample size is needed to further elucidate treatment effects.

scholarly journals SILDENAFIL IS NOT PROTECTIVE TO THE BOWEL FOLLOWING INTESTINAL ISCHEMIA AND REPERFUSION INJURY

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Hannah M. Moore, BS ◽  
Natalie A. Drucker, M.D. ◽  
Troy A. Markel, M.D
Keyword(s):  
Reperfusion Injury ◽  
Intestinal Ischemia ◽  
Acute Mesenteric Ischemia ◽  
Doppler Imaging ◽  
Cellular Damage ◽  
Vehicle Group ◽  
Ischemia And Reperfusion ◽  
Ischemia And Reperfusion Injury ◽  
Midline Laparotomy ◽  
Mesenteric Perfusion

Background and Hypothesis:  Acute Mesenteric Ischemia (AMI) occurs when blood supply to the intestine is decreased. This can lead to intestinal ischemia, cellular damage, necrosis, and if corrected, subsequent reperfusion injury. There are currently no medical treatments to help reverse ischemia and reperfusion injury (I/R) and, therefore novel treatments are necessary. Sildenafil, a compound that increases endogenous nitric oxide (NO) by blocking the phosphodiesterase-5 induced breakdown of cGMP, may function as a potent mesenteric vasodilator.  We therefore hypothesized that sildenafil would improve mesenteric perfusion during a mouse model of intestinal I/R.   Experimental Design or Project Methods:  Adult male C57Bl6J mice were anesthetized with isoflurane and a midline laparotomy performed. The base of the superior mesenteric artery was occluded with a non-crushing vascular clamp for 60 minutes. At the end of ischemia, sildenafil (1mg/kg, 10mg/kg, or 100mg/kg) or a PBS vehicle control were administered via intraperitoneal injection. Animals were then allowed to recover.  Twenty-four hours after ischemia, animals underwent assessment of mesenteric perfusion by Laser-Doppler imaging. Animals were then euthanized.  Perfusion was expressed as a percentage of baseline, depicted as mean +/- SEM, and analyzed by ANOVA.  P<0.05 was significant.  Results:  There were no significant differences in mesenteric perfusion between the vehicle group or any of the therapeutic groups.  (PBS: 53.03±11.35%; Sildenafil-low: 59.59±7.55%; Sildenafil-medium: 70.51±8.49; Sildenafil-high: 66.4±10.2, p=0.61).   Conclusion:  Sildenafil does not appear to be an effective treatment for improving mesenteric perfusion following intestinal ischemia. Further studies are required to determine the reasons for the ineffectiveness of sildenafil.  One possible explanation for these observations could be a lack of PGE5 in the intestinal vascular endothelium.   

scholarly journals Hydrogen sulfide improves intestinal recovery following ischemia by endothelial nitric oxide-dependent mechanisms

2017 ◽  
Vol 312 (5) ◽  
pp. G450-G456 ◽  
Author(s):  
Amanda R. Jensen ◽  
Natalie A. Drucker ◽  
Sina Khaneki ◽  
Michael J. Ferkowicz ◽  
Troy A. Markel
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Mucosal Injury ◽  
Sodium Hydrosulfide ◽  
Midline Laparotomy ◽  
Mesenteric Root ◽  
Mesenteric Perfusion ◽  
Endothelial Nitric Oxide

Hydrogen sulfide (H2S) is an endogenous gasotransmitter that has vasodilatory properties. It may be a novel therapy for intestinal ischemia-reperfusion (I/R) injury. We hypothesized that 1) H2S would improve postischemic survival, mesenteric perfusion, mucosal injury, and inflammation compared with vehicle and 2) the benefits of H2S would be mediated through endothelial nitric oxide. C57BL/6J wild-type and endothelial nitric oxide synthase knockout (eNOS KO) mice were anesthetized, and a midline laparotomy was performed. Intestines were eviscerated, the small bowel mesenteric root identified, and baseline intestinal perfusion was determined using laser Doppler. Intestinal ischemia was established by temporarily occluding the superior mesenteric artery. Following ischemia, the clamp was removed, and the intestines were allowed to recover. Either sodium hydrosulfide (2 nmol/kg or 2 µmol/kg NaHS) in PBS vehicle or vehicle only was injected into the peritoneum. Animals were allowed to recover and were assessed for mesenteric perfusion, mucosal injury, and intestinal cytokines. P values < 0.05 were significant. H2S improved mesenteric perfusion and mucosal injury scores following I/R injury. However, in the setting of eNOS ablation, there was no improvement in these parameters with H2S therapy. Application of H2S also resulted in lower levels of intestinal cytokine production following I/R. Intraperitoneal H2S therapy can improve mesenteric perfusion, intestinal mucosal injury, and intestinal inflammation following I/R. The benefits of H2S appear to be mediated through endothelial nitric oxide-dependent pathways. NEW & NOTEWORTHY H2S is a gaseous mediator that acts as an anti-inflammatory agent contributing to gastrointestinal mucosal defense. It promotes vascular dilation, mucosal repair, and resolution of inflammation following intestinal ischemia and may be exploited as a novel therapeutic agent. It is unclear whether H2S works through nitric oxide-dependent pathways in the intestine. We appreciate that H2S was able to improve postischemic recovery of mesenteric perfusion, mucosal integrity, and inflammation. The beneficial effects of H2S appear to be mediated through endothelial nitric oxide-dependent pathways.

Mechanisms of Nickel-Induced Cell Damage in Allergic Contact Dermatitis and Nutritional Intervention Strategies

2020 ◽  
Vol 20 (7) ◽  
pp. 1010-1014 ◽  
Author(s):  
Dana Filatova ◽  
Christine Cherpak
Keyword(s):  
Lipid Peroxidation ◽  
Contact Dermatitis ◽  
Oxidative Damage ◽  
Allergic Contact Dermatitis ◽  
Cell Damage ◽  
Consumer Products ◽  
The Body ◽  
Cellular Damage ◽  
Nutritional Interventions ◽  
Allergic Contact

Background: Hypersensitivity to nickel is a very common cause of allergic contact dermatitis since this metal is largely present in industrial and consumer products as well as in some commonly consumed foods, air, soil, and water. In nickel-sensitized individuals, a cell-mediated delayed hypersensitivity response results in contact to dermatitis due to mucous membranes coming in long-term contact with nickel-containing objects. This process involves the generation of reactive oxidative species and lipid peroxidation-induced oxidative damage. Immunologically, the involvement of T helper (h)-1 and Th-2 cells, as well as the reduced function of T regulatory cells, are of importance. The toxicity, mutagenicity, and carcinogenicity of nickel are attributed to the generation of reactive oxygen species and induction of oxidative damage via lipid peroxidation, which results in DNA damage. Objective: The aim of this research is to identify nutritionally actionable interventions that can intercept nickel-induced cell damage due to their antioxidant capacities. Conclusion: Nutritional interventions may be used to modulate immune dysregulation, thereby intercepting nickel-induced cellular damage. Among these nutritional interventions are a low-nickel diet and an antioxidant-rich diet that is sufficient in iron needed to minimize nickel absorption. These dietary approaches not only reduce the likelihood of nickel toxicity by minimizing nickel exposure but also help prevent oxidative damage by supplying the body with antioxidants that neutralize free radicals.

Desiccation Tolerance: Avoiding Cellular Damage During Drying and Rehydration

2020 ◽  
Vol 71 (1) ◽  
pp. 435-460 ◽  
Author(s):  
Melvin J. Oliver ◽  
Jill M. Farrant ◽  
Henk W.M. Hilhorst ◽  
Sagadevan Mundree ◽  
Brett Williams ◽  
...  
Keyword(s):  
Desiccation Tolerance ◽  
Cell Damage ◽  
Cellular Responses ◽  
Land Plants ◽  
Cellular Damage ◽  
Cellular Protection ◽  
Vegetative Tissues ◽  
Tolerant Plants ◽  
Core Set ◽  
Protection Mechanisms

Desiccation of plants is often lethal but is tolerated by the majority of seeds and by vegetative tissues of only a small number of land plants. Desiccation tolerance is an ancient trait, lost from vegetative tissues following the appearance of tracheids but reappearing in several lineages when selection pressures favored its evolution. Cells of all desiccation-tolerant plants and seeds must possess a core set of mechanisms to protect them from desiccation- and rehydration-induced damage. This review explores how desiccation generates cell damage and how tolerant cells assuage the complex array of mechanical, structural, metabolic, and chemical stresses and survive.Likewise, the stress of rehydration requires appropriate mitigating cellular responses. We also explore what comparative genomics, both structural and responsive, have added to our understanding of cellular protection mechanisms induced by desiccation, and how vegetative desiccation tolerance circumvents destructive, stress-induced cell senescence.

Surfactant toxicity in a case of (4-chloro-2-methylphenoxy) acetic acid herbicide intoxication

2014 ◽  
Vol 34 (8) ◽  
pp. 848-855 ◽  
Author(s):  
I Hwang ◽  
JW Lee ◽  
JS Kim ◽  
HW Gil ◽  
HY Song ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Cell Viability ◽  
Cell Damage ◽  
Neuronal Cell ◽  
University Hospital ◽  
Cellular Damage ◽  
Polypropylene Glycol ◽  
Toxic Symptom ◽  
Diphenyltetrazolium Bromide ◽  
Low Cytotoxicity

Objective: Self-poisoning with (4-chloro-2-methylphenoxy) acetic acid (MCPA) is a common reason for presentation to hospitals, especially in some Asian countries. We encountered a case of a 76-year-old woman who experienced unconsciousness, shock and respiratory failure after ingesting 100 mL MCPA herbicide. We determined whether the surfactant in the formulation was the chemical responsible for the toxic symptom in this patient. Design: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability and lactate dehydrogenase (LDH) cytotoxicity assays were performed on human brain neuroblastoma SK-N-SH cells. The expressions of 84 genes in 9 categories that are implicated in cellular damage pathways were quantified using an RT2 Profiler™ PCR array on a human neuronal cell line challenged with polyoxyethylene tridecyl ether (PTE). Setting: Pesticide intoxication institute in university hospital. Interventions: Extracorporeal elimination with intravenous lipid emulsion. Measurements: Cell viability and gene expression. Main Results: In the MTT assay, MCPA only minimally decreased cell viability even at concentrations as high as 1 mM. Cells treated with 1-methoxy-2-propanol, dimethylamine and polypropylene glycol exhibited minimal decreases in viability, whilst the viability of cells challenged with PTE decreased dramatically; only 15.5% of cells survived after exposure to 1 µM PTE. Similarly, the results of the LDH cytotoxicity assay showed that MCPA had very low cytotoxicity, whilst cells treated with PTE showed incomparably higher LDH levels ( p < 0.0001). PTE up-regulated the expressions of genes implicated in various cell damage pathways, particularly genes involved in the inflammatory pathway. Conclusions: The surfactant PTE was likely the chemical responsible for the toxic symptom in our patient.

scholarly journals Alternaria spp. IN FOODS: MYCOTOXINS, CELLULAR DAMAGE AND POSSIBLE HEALTH RISK

2018 ◽  
Vol 15 (30) ◽  
pp. 19-26
Author(s):  
F. P. de ANDRADE JUNIOR ◽  
T. W. B. ALVES ◽  
M. H. P. de LIRA ◽  
M. E. da S. MENEZES ◽  
I. O. LIMA
Keyword(s):  
Fruits And Vegetables ◽  
Cell Damage ◽  
Food Contamination ◽  
Great Majority ◽  
Fungal Species ◽  
Cellular Damage ◽  
Food Storage ◽  
Economic Losses ◽  
Teratogenic Action ◽  
Species Being

The genus Alternaria is composed of filamentous, dematiaceous, saprophytic and pathogenic fungal species, being responsible for great economic losses during the harvest and food storage. The present study aimed to do a bibliographical survey about the main foods contaminated by Alternaria spp. as well as discuss possible health risks arising from cell damage caused by mycotoxins. It is a literature narrative type review, carried out using Medline/Pubmed, Lilacs, Scielo and Science Direct databases, utilizing documents published between years 2000 and 2017 approaching food contamination by Alternaria spp. A wide diversity of foods contaminated by species of the genus Alternaria was found in literature, with a greater emphasis on cereals, fruits and vegetables. This possible contamination may favor the development of mycotoxins that in their great majority present genotoxic, mutagenic, carcinogenic, cytotoxic and teratogenic action. However, due to a large variety of contaminated foods, that is a necessity to adapt Brazilian legislation regarding parameters that impose limits on the amount of mycotoxins produced by Alternaria spp. since the national legislation does not encompass limits for all types of toxins that this genus is capable of producing.

scholarly journals Characterization of the Oxidative Stress in Renal Ischemia/Reperfusion-Induced Cardiorenal Syndrome Type 3

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Wellington Caio-Silva ◽  
Danielle da Silva Dias ◽  
Carolina Victoria Cruz Junho ◽  
Karine Panico ◽  
Raquel Silva Neres-Santos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Redox Balance ◽  
Renal Ischemia ◽  
Cellular Damage ◽  
Cellular Mechanisms ◽  
Inflammatory Conditions

In kidney disease (KD), several factors released into the bloodstream can induce a series of changes in the heart, leading to a wide variety of clinical situations called cardiorenal syndrome (CRS). Reactive oxygen species (ROS) play an important role in the signaling and progression of systemic inflammatory conditions, as observed in KD. The aim of the present study was to characterize the redox balance in renal ischemia/reperfusion-induced cardiac remodeling. C57BL/6 male mice were subjected to occlusion of the left renal pedicle, unilateral, for 60 min, followed by reperfusion for 8 and 15 days, respectively. The following redox balance components were evaluated: catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (FRAP), NADPH oxidase (NOX), nitric oxide synthase (NOS), hydrogen peroxide (H2O2), and the tissue bioavailability of nitric oxide (NO) such as S-nitrosothiol (RSNO) and nitrite (NO2−). The results indicated a process of renoprotection in both kidneys, indicated by the reduction of cellular damage and some oxidant agents. We also observed an increase in the activity of antioxidant enzymes, such as SOD, and an increase in NO bioavailability. In the heart, we noticed an increase in the activity of NOX and NOS, together with increased cell damage on day 8, followed by a reduction in protein damage on day 15. The present study concludes that the kidneys and heart undergo distinct processes of damage and repair at the analyzed times, since the heart is a secondary target of ischemic kidney injury. These results are important for a better understanding of the cellular mechanisms involved in CRS.

scholarly journals Predictive factors of intestinal necrosis in acute mesenteric ischemia

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 883-889 ◽  
Author(s):  
Alfonso Canfora ◽  
Antonio Ferronetti ◽  
Gianpaolo Marte ◽  
Vittorio Di Maio ◽  
Claudio Mauriello ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Organ Failure ◽  
Predictive Factors ◽  
Mesenteric Ischemia ◽  
Disease Risk ◽  
Acute Mesenteric Ischemia ◽  
Serum Lactate ◽  
Intestinal Necrosis ◽  
Ct Findings ◽  
Lactate Levels

AbstractObjectivesAcute mesenteric ischemia (AMI) is a gastrointestinal and vascular emergency in which the detection of patients requiring intestinal resection is mandatory.MethodsRegistered data of 55 consecutive patients admitted to our center between January 2010 and December 2016 that underwent an explorative laparotomy for a suspected diagnosis of irreversible transmural intestinal necrosis (ITIN) were analyzed. Demographic, clinical, laboratory and CT findings were statistically analyzed in order to search predictive factors of ITIN and their correlation to its clinical spectre.ResultsTobacco use was the most statistically significant (p<0.01) cardiovascular disease risk factor involved in ITIN. Among lab tests, Serum lactate levels ˃ 2mmol/L resulted in a statistically significant association with ITIN (p=0.0001). Organ failure (defined as Marshall score> 2) and the three main CT findings (decreased bowel wall enhancement, bowel loop dilation and demonstrated vessel occlusion) were strongly associated with ITIN (p values: 0.001, 0.007, 0.0013, 0.0005). Only serum lactate levels>2 mmol/L resulted as statistically significant as predictive factors of ITIN in multivariate analysis using logistic regression (OR 49.66 and p-value 0.0021).ConclusionOur univariate and multivariate analysis identified multiple factors (Serum lactate levels ˃ 2mmol/L, Organ failure, CT signs) that could suggest patients that require a surgical approach for ITIN.

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