Tranilast pre-treatment attenuates intestinal ischemia repercussion injury
E. Canovai, L. Ceulemans, G. de Hertogh, R. Farré, T. Vanuytsel
Thursday 15 march 2018
12:30 - 12:40h
at Van Weelde Zaal
Categories: Basic / translational research, Session (parallel)
Parallel session: Parallel session 2: Basic / translational research
Introduction
Intestinal ischemia reperfusion injury (IIRI) is unavoidable during intestinal transplantation and contributes to poor outcomes. Tranilast (TL) is a medication used for the treatment of rheumatoid arthritis, Crohn’s disease and severe atopic dermatitis. Given its anti-inflammatory and anti-oxidant properties, we hypothesized that TL may reduce IIRI in a rat model.
Methods/Materials
In a validated rat model of IIRI (isolated clamping of the superior mesenteric artery), 3 groups were tested: 1/Sham (laparotomy only); 2/ TL + 60’ Ischemia + 60’ reperfusion; 3/Vehicle + 60’ Ischemia + 60’ reperfusion (6/group). At the end of this period, the animals were sacrificed by exsanguination under anesthesia. To measure survival, 10 additional animals per group underwent the same procedure and 7-day survival was recorded. TL (650 gk/g) was administered by oral gavage 24 and 3 hours before IIRI. The endpoints were: histology (Park/Chiu score), plasma biomarkers for enterocyte damage (L-lactate, I-FABP), intestinal permeability (Ussing chamber), tissue pro- and anti-inflammatory cytokines (RT-PCR), endotoxin translocation (Limulus Amebocyte Lysate Pyrogent kit), HO-1 protein (Western blot) and 7-day survival.
Results
IIRI led to severe damage of the intestinal wall, both structurally and functionally. These alterations were linked with increased endotoxin plasma levels and upregulation of pro-inflammatory cytokine in tissue. TL pre-treatment attenuated these parameters and improved 7-day survival (see Table) and upregulated HO-1 expression. Blocking HO-1 expression nullified the protective effect of Tranilast.
Conclusion
Tranilast pre-treatment improves intestinal permeability, reduces inflammation, lowers endotoxin translocation and improves survival probably via HO-1 upregulation.
