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Aim: To assess the feasibility of SPECT-computed tomography (CT) in rats with trinitrobenzene sulfonic acid (TNBS)-induced acute colitis and confront it with model inflammatory characteristics., Methods: Colitis was induced in Sprague-Dawley rats by intrarectal injection of TNBS ( n = 10) while controls received vehicle ( n = 10). SPECT-CT with intravenous injection of 10 MBq of 67Ga-Citrate was performed at day 2. SPECT-CT criteria were colon wall thickness and maximal wall signal intensity. Laboratory parameters were assessed: colon weight:length ratio, colon cyclooxygenase-2 expression by western blot and histological inflammatory score., Results: Colon weight/length ratio, colon COX-2 expression and histological inflammatory score were significantly higher in the TNBS group than in the control group ( P = 0.0296, P < 0.0001, P = 0.0007 respectively). Pixel max tend to be higher in the TNBS group than in the control group but did not reach statistical significance ( P = 0.0662). Maximal thickness is significantly increased in the TNBS group compared to the control group ( P = 0.0016) while colon diameter is not ( P = 0.1904). Maximal thickness and colon diameter were correlated to colon COX-2 expression ( P = 0.0093, P = 0.009 respectively) while pixel max was not ( P = 0.22). Maximal thickness was significantly increased when inflammation was histologically observed ( P = 0.0043) while pixel max and colon diameter did not ( P = 0.2452, P = 0.3541, respectively)., Conclusion: SPECT-CT is feasible and easily distinguished control from colitic rats., Competing Interests: Conflict-of-interest statement: We declare that we have no financial and personal relationships with other people or organizations that could inappropriately influence our work.

Aim: To investigate whether targeting proteasome might reverse intestinal fibrosis in rats., Methods: Chronic colitis was induced in rats by repeated administration of increasing dose of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 15, 30, 45, 60, 60, 60 mg) by rectal injection for 6 wk (from day 0 to day 35), while control rats received the vehicle. TNBS + bortezomib (BTZ) rats received intraperitoneal injections of BTZ twice weekly (from day 37 to day 44) at a dose of 25 mg/kg, whereas the control and TNBS groups received the same amount of the vehicle. Histologic scoring of inflammation and fibrosis was performed. Colonic production of transforming growth factor (TGF)-β was measured by ELISA. Colon fibrosis-related proteins such as phospho-p38, phospho-SMAD2/3, Akt and peroxisome proliferator activated receptor γ (PPARγ) were studied by western blot. Expression of the tight junction proteins, occludin and claudin-1, were assessed by Western blot. Colon proteasome activities (chymotrypsin-like and trypsin-like activities) were assessed., Results: TNBS-treated rats had a higher colon weight/length ratio compared to control rats (P < 0.01). Furthermore, fibrosis and inflammation scores were higher in TNBS-treated rats compared to control rats (P < 0.01 for both). Colonic production of TGF-β production tended to be higher in TNBS-treated rats (P < 0.06). Fibrosis-related proteins such as phospho-p38, phospho-SMAD2/3, and PPARγ were significantly higher in TNBS-treated rats compared to control rats (all P < 0.05). TNBS rats had a higher expression of Akt compared to control rats (P < 0.01). Tight junction proteins were modified by repeated TNBS challenge: colon occludin expression rose significantly (P < 0.01), whereas claudin-1 expression fell (P < 0.01). Bortezomib inhibition significantly decreased chymotrypsin-like activity (P < 0.05), but had no significant effect on trypsin-like activity (P > 0.05). In contrast, bortezomib had no effect on other studied parameters such as fibrosis score, TGF-β signaling, or tight junction expression (P > 0.05 for all)., Conclusion: Rats with TNBS-induced chronic colitis exhibited colon fibrosis associated with higher TGF-β signaling. Proteasome inhibition by bortezomib had no effect on fibrosis in our experimental conditions.