scholarly journals Translational Application of Fluorescent Molecular Probes for the Detection of Reactive Oxygen and Nitrogen Species Associated with Intestinal Reperfusion Injury

Metabolites ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 802
Author(s):  
Gustavo Sampaio de Holanda ◽  
Samuel dos Santos Valença ◽  
Amabile Maran Carra ◽  
Renata Cristina Lopes Lichtenberger ◽  
Bianca de Castilho ◽  
...  

Acute mesenteric ischemia, caused by an abrupt interruption of blood flow in the mesenteric vessels, is associated with high mortality. When treated with surgical interventions or drugs to re-open the vascular lumen, the reperfusion process itself can inflict damage to the intestinal wall. Ischemia and reperfusion injury comprise complex mechanisms involving disarrangement of the splanchnic microcirculatory flow and impairment of the mitochondrial respiratory chain due to initial hypoxemia and subsequent oxidative stress during the reperfusion phase. This pathophysiologic process results in the production of large amounts of reactive oxygen (ROS) and nitrogen (RNS) species, which damage deoxyribonucleic acid, protein, lipids, and carbohydrates by autophagy, mitoptosis, necrosis, necroptosis, and apoptosis. Fluorescence-based systems using molecular probes have emerged as highly effective tools to monitor the concentrations and locations of these often short-lived ROS and RNS. The timely and accurate detection of both ROS and RNS by such an approach would help to identify early injury events associated with ischemia and reperfusion and increase overall clinical diagnostic sensitivity. This abstract describes the pathophysiology of intestinal ischemia and reperfusion and the early biological laboratory diagnosis using fluorescent molecular probes anticipating clinical decisions in the face of an extremely morbid disease.

2020 ◽  
Author(s):  
Rui Wang ◽  
Teng Pan ◽  
Lin Huang ◽  
Chengde Liao ◽  
Qinqing Li ◽  
...  

Abstract Purpose: It is still a challenge to distinguish whether the damaged intestine is viable or not in the treatment of acute mesenteric ischemia. In this study, photoacoustic imaging (PAI) was used to observe the activity of intestinal tissue after ischemia and reperfusion injury in rats.Methods: With the approval of animal ethics committee our university, in vivo study was carried out. Forty male SD rats were randomly divided into four groups: sham operated (SO) group, 1 h ischemia group, 2 h ischemia group and ischemia-reperfusion (I/R) group. In the ischemia group, superior mesenteric artery (SMA) was isolated and clamped for 1 h (n = 10) and 2 h (n = 10), respectively. In I/R group, after ischemia for 1 hour, the clamp was removed and reperfused for 1 hour (n = 10). The same time interval of SMA was taken as SO group (n = 10). Immediately after the establishment of the animal model, PAI examination was performed. After PAI examination, the small intestine was collected for histopathology.Results: The PAI derived parameters of 2 h ischemia group were significantly different from those of SO group and I/R group (P < 0.05). The levels of Hb, HbR, map760 and map 840 were increased in different degrees in ischemia group, especially in 2 h ischemia group (compared with SO group, P < 0.01). With the prolongation of ischemia time, the injury was aggravated. In immunohistochemistry, compared with SO group, BAX increased significantly in 2 h ischemia group (P < 0.01). Similarly, Caspase-3 was significantly higher than the baseline level (P < 0.05). The level of HIF-1a increased in 2 h ischemia group and I/R group (P < 0.05). TUNEL staining showed that the number of apoptotic positive nuclei in 2 h ischemia group was significantly higher than that in SO group (P < 0.05). HE staining showed that ischemia for 2 hours was the most serious, with obvious mucosal damage, extensive epithelial injury and bleeding.Conclusions: PAI can be used as an effective tool to detect acute intestinal ischemia injury and quantitatively evaluate tissue viability.


2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Hannah M. Moore, BS ◽  
Natalie A. Drucker, M.D. ◽  
Troy A. Markel, M.D

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.   


2020 ◽  
Vol 16 ◽  
Author(s):  
Andrey Krylatov ◽  
Leonid Maslov ◽  
Sergey Y. Tsibulnikov ◽  
Nikita Voronkov ◽  
Alla Boshchenko ◽  
...  

: There is considerable evidence in the heart that autophagy in cardiomyocytes is activated by hypoxia/reoxygenation (H/R) or in hearts by ischemia/reperfusion (I/R). Depending upon the experimental model and duration of ischemia, increases in autophagy in this setting maybe beneficial (cardioprotective) or deleterious (exacerbate I/R injury). Aside from the conundrum as to whether or not autophagy is an adaptive process, it is clearly regulated by a number of diverse molecules including reactive oxygen species (ROS), various kinases, hydrogen sulfide (H2S) and nitric oxide (NO). The purpose this review is to address briefly the controversy regarding the role of autophagy in this setting and to examine a variety of disparate molecules that are involved in its regulation.


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