Figure 6.

Inhibition of CFTR and iNOS activity ameliorates diarrhea in colitis models. A: The experimental design to test the effect of a CFTR channel blocker CFTR_inh-172 on fluid secretion in a mouse DSS colitis model. Line graph shows the total body weight measurements over a period of 7 days of mice in experimental groups: saline ± DSS treatment and CFTR_inh-172 ± DSS. Representative isolated mouse colons with no DSS ± CFTR_inh-172 and DSS ± CFTR_inh-172 treatment. Arrows show the extent of fluid secretion in the colon. Middle and right bar graphs show the assessments of various disease variables of the DSS-induced colitis, including stool score and wet/dry weight ratio of the fecal pellets in the mice not receiving or receiving intraperitoneal injection of CFTR_inh-172. B: The experimental design to test the effect of L-NIL on fluid secretion in a mouse DSS colitis model. Representative isolated mouse colons of the treatment group: DSS ± L-NIL to visualize gross fluid accumulation in the colon corresponding to day 1 L-NIL treatment. Arrows show the extent of fluid accumulation in the colon. Line graph shows the total body weight measurements over a period of 7 days for the experimental groups as follows: control + saline, control + L-NIL (day 1), DSS + saline, DSS + L-NIL (day 1 to 3). Middle and right bar graphs show the assessments of various disease variables of the DSS-induced colitis, including stool score and wet/dry weight ratio of the fecal pellets in the mice not receiving or receiving intraperitoneal injection L-NIL (cumulative data of DSS + L-NIL treatment group). C: Bar graph represents nitrite (left) and cGMP levels (right) in colon tissues in response to DSS and DSS + LNIL treatment. Data are expressed as means ± SEM. n = 4 experimental groups (A); n = 3 mice each in no DSS treatment group and control group (A); n = 5 to 8 mice in DSS treatment group (A); n = 7 to 8 mice per group for CFTR_inh-172 treatment (A); n = 5 experimental groups (B); n = 4 to 5 mice per DSS treatment group (B); n = 3 colon tissue samples (C). ^∗P < 0.05, ^∗∗P < 0.01, and ^∗∗∗P < 0.001 determined with t-test. Significance of intergroup variance was evaluated with one-way analysis of variance for CFTR and iNOS inhibition animal experiments. CFTR, cystic fibrosis transmembrane-conductance regulator; CFTR_inh-172, thiozolidinone CFTR inhibitor; DSS, dextran sodium sulfate; iNOS, inducible nitric oxide synthase; L-NIL, N⁶-(1-Iminoethyl)-l-lysine dihydrochloride.