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

COX-2 抑制剂与抗氧化疗法的新组合,用于调节与肠缺血再灌注损伤和内毒血症相关的氧化应激

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

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.

Conclusions

Our results indicate that this approach could be a new pharmacological protocol for intestinal colic or ischemic injury-induced endotoxemia.

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.

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