Ischemic Preconditioning and Tacrolimus Pretreatment as Strategies to Attenuate Intestinal Ischemia-Reperfusion Injury in Mice

• Published in: Transplantation proceedings 2013-07, Vol.45 (6), p.2480-2485
• Main Authors: Stringa, P, Romanin, D, Lausada, N, Machuca, M, Raimondi, J.C, Cabanne, A, Rumbo, M, Gondolesi, G
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers - metabolism; Combined Modality Therapy; Disease Models, Animal; Immunosuppressive Agents - pharmacology; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Intestinal Diseases - etiology; Intestinal Diseases - metabolism; Intestinal Diseases - pathology; Intestinal Diseases - prevention & control; Intestines - blood supply; Intestines - drug effects; Intestines - metabolism; Intestines - pathology; Ischemic Preconditioning; Lung - drug effects; Lung - pathology; Male; Mice; Mice, Inbred BALB C; Nitrites - metabolism; Reperfusion Injury - etiology; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Surgery; Tacrolimus - pharmacology; Time Factors; Warm Ischemia - adverse effects
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2013.02.113

Abstract The intestine is highly sensitive to ischemia-reperfusion injury (IRI), a phenomenon occurring in different intestinal diseases. Several strategies to mitigate IRI are in experimental stages; unfortunately, no consensus has been reached about the most appropriate one. We report a protocol to study ischemic preconditioning (IPC) evaluation in mice and to combine IPC and tacrolimus (TAC) pretreatment in a warm ischemia model. Mice were divided into treated (IPC, TAC, and IPC + TAC) and untreated groups before intestinal ischemia. IPC, TAC, and IPC + TAC groups were able to decrease postreperfusion nitrites levels ( P  < .05). IPC-containing groups had a major beneficial effect by preserving the integrity of the intestinal histology ( P  < .05) and improving animal survival ( P  < .002) compared with TAC alone or the untreated group. The IPC + TAC group was the only one that showed significant improvement in lung histological analysis ( P  < .05). The TAC and IPC + TAC groups down-regulated intestinal expression of interleukin (II)-6 and IL1b more than 10-fold compared with the control group. Although IPC and TAC alone reduced intestinal IRI, the used of a combined therapy produced the most significant results in all the local and distant evaluated parameters.