Novel Combination of COX-2 Inhibitor and Antioxidant Therapy for Modulating Oxidative Stress Associated with Intestinal Ischemic Reperfusion Injury and Endotoxemia.

Enrico Gugliandolo,Marika Cordaro,Salvatore Cuzzocrea,Alessio Filippo Peritore,Daniela Impellizzeri,Rosanna Di Paola,Tiziana Genovese,Rosalba Siracusa,Ramona D’Amico,Roberta Fusco,Rosalia Crupi

doi:10.3390/antiox9100930

Enrico Gugliandolo, Marika Cordaro + Show 9 more

Open Access

https://doi.org/10.3390/antiox9100930

Copy DOI

Journal: Antioxidants	Publication Date: Sep 28, 2020
Citations: 7	License type: CC BY 4.0

Affiliation: University of Messina, Saint Louis University

Abstract

Background: Intestinal ischemic reperfusion (I/R) injury is associated with a high mortality rate; this condition is also related to significant endotoxemia and systemic inflammation. The preservation of tissue perfusion and a sufficient blood flow are required to deliver nutrients and oxygen, preserve metabolic pathways, and eliminate waste products. Oxidative stress plays a fundamental role in intestinal I/R injury and leads to disruption of the mucosal barrier and necrosis, allowing the migration of endotoxins and luminal bacteria into the systemic circulation. In this study, we evaluated the beneficial effects of a cyclooxygenase (COX)-2 inhibitor—firocoxib—plus the antioxidant vitamin C in a rat model of intestinal I/R injury. Methods: We used a rat model of I/R injury in which the superior mesenteric artery was clamped for 30 min by a vascular clamp, and the animals were then allowed 1 h of reperfusion. Results: Our results show the importance of combined anti-inflammatory and antioxidant treatment for the prevention of intestinal I/R injury that leads to reduced systemic endotoxemia. We observed a significantly synergistic effect of firocoxib and vitamin C in reducing intestinal wall damage and oxidative stress, leading to a significant reduction of inflammation and endotoxemia. Conclusions: Our results indicate that this approach could be a new pharmacological protocol for intestinal colic or ischemic injury-induced endotoxemia.

Highlights

Intestinal obstruction has been defined as simultaneous vascular and luminal damage that can be of ischemic or hemorrhagic origin [1]
An intense shock state is associated with an increased mortality at the end of the reperfusion period (Figure 1B, Supplemental Figure S1)
The combined administration of both was able to downregulate COX-2 and PGE2 expression. This combined therapy increased the endogenous antioxidant systems. Endogenous antioxidant systems such as catalase, superoxide dismutase, and glutathione peroxidase protect against oxidant injury [37]

Summary

Introduction

Intestinal obstruction has been defined as simultaneous vascular and luminal damage that can be of ischemic or hemorrhagic origin [1]. It leads to disruption of the intestinal barrier function, hypovolemia, endotoxemia, and cytotoxic shock [2]. Intensive medical therapy, and supportive care, the perioperative mortality is high This is likely a reflection of the severe damage the intestine sustains during the ischemic period and the further injury that occurs upon reperfusion. Oxidative stress plays a fundamental role in intestinal I/R injury and leads to disruption of the mucosal barrier and necrosis, allowing the migration of endotoxins and luminal bacteria into the systemic circulation. Methods: We used a rat model of I/R injury in which the superior mesenteric artery was clamped for 30 min by a vascular clamp, and the animals were allowed 1 h of reperfusion

Objectives

Methods

Results

Discussion

Conclusion