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,
Rosalba Siracusa,
Ramona D’Amico,
Alessio Filippo Peritore,
Tiziana Genovese,
Daniela Impellizzeri,
Rosanna Di Paola,
Rosalia Crupi,
Salvatore Cuzzocrea,
Roberta Fusco
Affiliations
Enrico Gugliandolo
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Marika Cordaro
Department of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, Via Consolare Valeria, 98125 Messina, Italy
Rosalba Siracusa
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Ramona D’Amico
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Alessio Filippo Peritore
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Tiziana Genovese
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Daniela Impellizzeri
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Rosanna Di Paola
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Rosalia Crupi
Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy
Salvatore Cuzzocrea
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Roberta Fusco
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
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.
