{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:38:35Z","timestamp":1790797115682,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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\u2014firocoxib\u2014plus 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.<\/jats:p>","DOI":"10.3390\/antiox9100930","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T20:03:02Z","timestamp":1601323382000},"page":"930","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Novel Combination of COX-2 Inhibitor and Antioxidant Therapy for Modulating Oxidative Stress Associated with Intestinal Ischemic Reperfusion Injury and Endotoxemia"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6840-3154","authenticated-orcid":false,"given":"Enrico","family":"Gugliandolo","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3980-0043","authenticated-orcid":false,"given":"Marika","family":"Cordaro","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, Via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7868-2505","authenticated-orcid":false,"given":"Rosalba","family":"Siracusa","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0389-3871","authenticated-orcid":false,"given":"Ramona","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8545-990X","authenticated-orcid":false,"given":"Alessio Filippo","family":"Peritore","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Genovese","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9492-3161","authenticated-orcid":false,"given":"Daniela","family":"Impellizzeri","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6725-8581","authenticated-orcid":false,"given":"Rosanna Di","family":"Paola","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-3132","authenticated-orcid":false,"given":"Rosalia","family":"Crupi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6131-3690","authenticated-orcid":false,"given":"Salvatore","family":"Cuzzocrea","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"},{"name":"Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0223-1403","authenticated-orcid":false,"given":"Roberta","family":"Fusco","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0749-0739(17)30587-4","article-title":"The pathophysiology of intestinal damage: Effects of luminal distention and ischemia","volume":"5","author":"Snyder","year":"1989","journal-title":"Vet. 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