Journal of Inflammation Research (Sep 2023)
Prophylactic Treatment of Intestinal Ischemia-Reperfusion Injury Reduces Mucosal Damage and Improves Intestinal Absorption
Abstract
Ignacio Garcia-Alonso,1,2,* Xabier Velasco-Oraa,3,* Iñigo Cearra,1,4,5 Sira Iturrizaga Correcher,6 Carmen Mar Medina,6 Ana Alonso-Varona,7 Amador García Ruiz de Gordejuela,1,8 Inmaculada Ruiz-Montesinos,1,8 Borja Herrero de la Parte1,2,* 1Department of Surgery and Radiology and Physical Medicine, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, 48940, Spain; 2Interventional Radiology Research Group, Biocruces Bizkaia Health Research Institute, Barakaldo, 48903, Spain; 3Department of Anaesthesia, Hospital Clínic of Barcelona, Barcelona, 08036, Spain; 4Department of Orthopedics, Basurto University Hospital, Osakidetza Basque Health Service, Bilbao, 48013, Spain; 5Regenerative Therapies, Osteoarticular and Tendon Pathology Research Group, Biocruces Bizkaia Health Research Institute, Barakaldo, 48903, Spain; 6Department of Clinical Analyses, Galdakao-Usansolo University Hospital, Galdakao, 48960, Spain; 7Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, 48940, Spain; 8Department of Gastrointestinal Surgery, Donostia University Hospital, Osakidetza Basque Health Service, Donostia, 20014, Spain*These authors contributed equally to this workCorrespondence: Borja Herrero de la Parte, Department of Surgery and Radiology and Physical Medicine, University of The Basque Country, Barrio Sarriena s/n, Leioa, 48940, Spain, Tel +34 946015590, Email [email protected]: Intestinal ischemia-reperfusion injury (i–IRI) involves a blood flow interruption in an intestinal segment followed by blood flow restoration. When blood flow is restored, oxidative and inflammatory molecules are distributed throughout the bloodstream, triggering both local and systemic damage. Our goal was to evaluate the potential of three antioxidant and/or anti–inflammatory compounds (curcumin, dexmedetomidine and α-tocopherol) to prevent or reverse local and systemic damage induced by i–IRI.Methods: i-IRI was induced by placing a microvascular clip in the superior mesenteric artery of female WAG/RijHsd rats; the clip was removed after 1h and reperfusion was allowed for 4h. Curcumin (200 mg/kg, orally), α-tocopherol (20 mg/kg, i.p.), and dexmedetomidine (5 or 20 μg/kg, s.c.; DEX5 and DEX20, respectively) were administered. Blood and terminal ileum specimens were collected for biochemical and histological determination. Furthermore, D-xylose absorption test was performed to evaluate intestinal absorption; after completing the 1-hour ischemia and 4-hour reperfusion period, 1 mL of aqueous D-xylose solution (0.615 mg/mL) was administered orally, and one hour later, plasma D-xylose levels were quantified.Results: The histological injury degree (HID) measured by the Chiu scale was significantly reduced when the treatments were applied (non-treated rats, 2.6 ± 0.75; curcumin, 1.54 ± 0.8; DEX5, 1.47 ± 0.7; DEX20 1.14 ± 0.5; and α-tocopherol, 1.01 ± 0.6); intestinal absorptive capacity also improved in all cases healthy rats (2.06 ± 0.07 μg/mL; non-treated, 1.18 ± 0.07 μg/mL; curcumin 1.76 ± 0.3 μg/mL; DEX5, 2.29 ± 0.2 μg/mL; DEX20, 2.25 ± 0.26 μg/mL; and α-tocopherol 1.66 ± 0.21 μg/mL). However, it failed to reduce liver enzyme levels. Finally, only dexmedetomidine significantly reduced urea and creatinine levels compared to non-treated animals.Conclusion: All drugs were effective in reducing HID, although α-tocopherol was effective to a greater extent. Only dexmedetomidine reverted intestinal absorption to normal values of healthy animals.Keywords: intestinal ischemia-reperfusion, i-IRI, female rat, α-tocopherol, curcumin, dexmedetomidine, intestinal mucosal damage, absorptive function, antioxidant therapy
