The use of animals to gain knowledge and understanding of diseases needs to be reduced and refined. In the field of intestinal research, because of the complexity of the gut immune system, living models testing is mandatory. Based on the 3Rs (replacement, reduction and refinement) principles, we aimed to developed and apply the derived-intestinal surgical procedure described by Bishop and Koop (BK) in rats to refine experimental gastrointestinal procedures and reduce the number of animals used for research employing two models of intestinal inflammation: intestinal ischemia-reperfusion injury and chemical-induced colitis. Our results show the feasibility of the application of the BK technique in rodents, with good success after surgical procedure in both small and large intestine (100% survival, clinical recovery and weight regain). A considerable reduction in the use of the number of rats in both intestinal inflammation models (80% in case of intestinal ischemia-reperfusion damage and 66.6% in chemical-induced colitis in our experimental design) was achieved. Compared with conventional experimental models described by various research groups, we report excellent reproducibility of intestinal damage and functionality, survival rate and clinical status of the animals when BK is applied.
RussellWMSBurchRLHumeCW.The principles of humane experimental technique.
London:
Methuen & Co., 1959, pp. 252.
2.
ValdiviesoA.Guía de Trasplantes de Órganos Abdominales. Guías Clínicas la Asoc Española Cir.
Madrid:
Arán, 2016.
3.
CarverTWVoraRSTanejaA.Mesenteric ischemia. Crit Care Clin2016;
32(2): 155–171.
4.
RotsteinOD.Pathogenesis of multiple organ dysfunction syndrome: gut origin, protection, and decontamination. Surg Infect (Larchmt)2000;
1: 217–225.
5.
GrootjansJLenaertsKBuurmanWA, et al.
Life and death at the mucosal-luminal interface: new perspectives on human intestinal ischemia-reperfusion. World J Gastroenterol2016;
22: 2760–2770.
6.
MallickIHYangWWinsletMC, et al.
Ischemia-reperfusion injury of the intestine and protective strategies against injury. Dig Dis Sci2004;
49: 1359–1377.
7.
LysyyTFinottiMMainaRM, et al.
Human small intestine transplantation: segmental susceptibility to ischemia using different preservation solutions and conditions. Transplant Proc2020;
52: 2934–2940.
8.
StringaPRomaninDLausadaN, et al.
Ischemic preconditioning and tacrolimus pretreatment as strategies to attenuate intestinal ischemia-reperfusion injury in mice. Transplant Proc2013;
45: 2480–2485.
9.
SileriPSicaGGentileschiP, et al.
Ischemic preconditioning protects intestine from prolonged ischemia. Transplant Proc2004;
36: 283–285.
10.
AksöyekSCinelIAvlanD, et al.
Intestinal ischemic preconditioning protects the intestine and reduces bacterial translocation. Shock (Augusta, Ga.)2002;
18: 476–480.
11.
IrapordaCRomaninDEBengoaAA, et al.
Local treatment with lactate prevents intestinal inflammation in the TNBS-induced colitis model. Front Immunol2016;
7: 651.
12.
AlexPZachosNCNguyenT, et al.
Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis. Inflamm Bowel Dis2003;
15: 341–352.
13.
ElhennawyMGAbdelaleemEAZakiAA, et al.
Cinnamaldehyde and hesperetin attenuate TNBS-induced ulcerative colitis in rats through modulation of the JAk2/STAT3/SOCS3 pathway. J Biochem Mol Toxicol2021;
35: e22730.
14.
Le BrasA.Gut microbiota drives disease variability in the DSS colitis mouse model. Lab Anim (NY)2022;
51: 131.
15.
Sampaio de HolandaGdos Santos ValençaSMaran CarraA, et al.
Sulforaphane and albumin attenuate experimental intestinal ischemia-reperfusion injury. J Surg Res2021;
262: 212–223.
16.
Ricardo-Da-silvaFYFantozziETRodrigues-GarbinS, et al.
Estradiol prevented intestinal ischemia and reperfusion-induced changes in intestinal permeability and motility in male rats. Clinics (Sao Paulo)2021;
76: e2683.
17.
ParlarAArslanSO.Thymoquinone reduces ischemia and reperfusion-induced intestinal injury in rats, through anti-oxidative and anti-inflammatory effects. Turkish J Surg2020;
36: 96–104.
18.
OrakCŞirinyıldızFGökmen YılmazE, et al.
Protective effects of ficus carica seed oil on ischemia and reperfusion injury in a rat model of acute mesenteric ischemia. Ulus Travma ve Acil Cerrahi Derg2021;
27: 402–409.
19.
TahirMArshidSFontesB, et al.
Phosphoproteomic analysis of rat neutrophils shows the effect of intestinal ischemia/reperfusion and preconditioning on kinases and phosphatases. Int J Mol Sci2020;
21: 5799.
20.
WanYDongPZhuX, et al.
Bibliometric and visual analysis of intestinal ischemia reperfusion from 2004 to 2022. Front Med2022;
9: 963104.
21.
DaiDDaiFChenJ, et al.
Integrated multi-omics reveal important roles of gut contents in intestinal ischemia–reperfusion induced injuries in rats. Commun Biol2022;
5: 938.
22.
FanSXuYLiK, et al.
Ellagic acid alleviates mice intestinal ischemia-reperfusion injury: a study based on transcriptomics combined with functional experiments. Chem Biodivers2022;
19: e202200345.
23.
AfolabiOAAkhigbeTMAkhigbeRE, et al.
Methanolic Moringa oleifera leaf extract protects against epithelial barrier damage and enteric bacterial translocation in intestinal I/R: possible role of caspase 3. Front Pharmacol2022;
13: 989023.
24.
LiuXYangBTanYF, et al.
The role of AMPK-Sirt1-autophagy pathway in the intestinal protection process by propofol against regional ischemia/reperfusion injury in rats. Int Immunopharmacol2022;
111: 109114.
25.
AfolabiAOAkhigbeTMOdetayoAF, et al.
Restoration of hepatic and intestinal integrity by Phyllanthus amarus is dependent on Bax/caspase 3 modulation in intestinal ischemia-/reperfusion-induced injury. Molecules2022;
27: 5073.
26.
PeresECVictorioJANunes-SouzaV, et al.
Simvastatin protects against intestinal ischemia/reperfusion-induced pulmonary artery dysfunction. Life Sci2022;
306: 120851.
27.
AkıncıOTosunYKepilN.The effect of genistein on anastomotic healing in intestinal ischemia/reperfusion injury. J Surg Res2022;
280: 389–395.
28.
NojimaTObaraTYamamotoH, et al.
Luminal administration of biliverdin ameliorates ischemia-reperfusion injury following intestinal transplant in rats. Surgery2022;
172: 1522–1528.
29.
OzbanMAydinCCevahirN, et al.
The effect of melatonin on bacterial translocation following ischemia/reperfusion injury in a rat model of superior mesenteric artery occlusion. BMC Surg2015;
15: 18.
30.
LiuYJXuWHFanLM, et al.
Polydatin alleviates DSS- and TNBS-induced colitis by suppressing Th17 cell differentiation via directly inhibiting STAT3. Phytother Res2022;
36: 3662–3671.
31.
LiGWuXGaoX, et al.
Long-term exclusive enteral nutrition remodels the gut microbiota and alleviates TNBS-induced colitis in mice. Food Funct2022;
13: 1725–1740.
32.
QiuJWuCGaoQ, et al.
Effect of fecal microbiota transplantation on the TGF-β1/Smad signaling pathway in rats with TNBS-induced colitis. Ann Transl Med2022;
10: 825–825.
33.
WangDLiSMaX, et al.
Immunomodulatory effects of fentanyl and morphine on DSS- and TNBS-induced colitis. Immunopharmacol Immunotoxicol2022;
44:1044–1057.
34.
HambardikarVRMandlikDS.Protective effect of naringin ameliorates TNBS‐induced colitis in rats via improving antioxidant status and pro-inflammatory cytokines. Immunopharmacol Immunotoxicol2022;
44: 373–386.
35.
HongCJChenSYHsuYH, et al.
Protective effect of fermented okara on the regulation of inflammation, the gut microbiota, and SCFAs production in rats with TNBS-induced colitis. Food Res Int2022;
157: 111390.
36.
SilvaIMendesPGuerraS, et al.
Anti-inflammatory effect of topiramate in a chronic model of TNBS-induced colitis. Int J Mol Sci2022;
23:9127.
37.
RoySDhaneshwarSMahmoodT, et al. Pre-clinical investigation of protective effect of nutraceutical d-glucosamine on TNBS-induced colitis. Immunopharmacol Immunotoxicol. Epub ahead of print 3 October 2022.
38.
BishopHCKoopCE.Management of meconium ileus. Ann Surg1957;
145: 404–414.
39.
SteeleLRMilburnCL Jr.Congenital atresia of the small intestine.U S Armed Forces Med J1952;
3:1731–1739.
40.
StringaPRomaninDLausadaN, et al.
Gut permeability and glucose absorption are affected at early stages of graft rejection in a small bowel transplant rat model. Transplant Direct2017;
3: e220.
41.
ParkPOHaglundUBulkleyGBFK. The sequence of development of intestinal tissue injury after strangulation ischemia and reperfusion. Surgery1990;
107: 574–80.
42.
ChiuC-J.Intestinal mucosal lesion in low-flow states. Arch Surg1970;
101: 478.
43.
SchindelinJArganda-CarrerasIFriseE, et al.
Fiji—an open platform for biological image analysis. Nat Methods2009;
9: 676–682.
44.
RomaninDELlopisSGenovésS, et al.
Probiotic yeast Kluyveromyces marxianus CIDCA 8154 shows anti-inflammatory and anti-oxidative stress properties in in vivo models. Benef Microbes2016;
7: 83–93.
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