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

Figure 4 Oral treatment with plecanatide ameliorates gastrointestinal inflammation in the dextran sulfate sodium-induced colitis in BDF1 mice. BDF1 mice (n = 8/group) were administered 5% DSS in drinking water. An oral gavage was administered once daily containing 0.005 to 5.0 mg/kg of plecanatide beginning a day prior to initiating DSS regimen. 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 colitis score ± SEM was plotted for the indicated treatment groups. Statistical significance was calculated by comparing severity scores observed for the plecanatide or sulfasalazine treated group vs corresponding values in the vehicle treated group. DSS: Dextran sulfate sodium; SEM: Standard error of the mean.