Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis

Figure 5 Oral treatment with plecanatide ameliorates gastrointestinal inflammation in 2, 4, 6-trinitrobenzenesulfonic acid-induced colitis in BDF1 mice. BDF1 mice (n = 10/group) were administered TNBS via rectal instillation on 0 d as described under Materials and Methods. An oral gavage was administered once daily containing 0.005 to 5.0 mg/kg plecanatide beginning a day prior to TNBS treatment. Sulfasalazine (80 mg/kg) and vehicle (phosphate buffer) served as positive and negative controls, respectively. At the end of the study mice were euthanized; distal sections of the colon were fixed, embedded in paraffin, sectioned, stained with H and E and visualized to assign colitis severity scores. All slides were scored in a blinded manner. The mean histological severity of the colitis score ± SEM was plotted for the indicated treatment groups. Statistical significance was calculated by comparing the severity score observed for the plecanatide or sulfasalazine-treated group vs the corresponding values in the vehicle-treated group. TNBS: 2, 4, 6-trinitrobenzenesulfonic acid sol; SEM: Standard error of the mean.