Figure 5.
NO-Related Metabolites Alleviate Colitis Severity
Treatment with arginine pathway-related metabolites leads to a significant improvement in colitis severity. Colitis was induced in wild-type C57BL/6J.OlaHsd mice. Mice were treated with DSS for 6 days, followed by administration of either arginine solution in drinking water, citrulline, or NaNO2 or with water as a control for an additional 6 days.
(A) Significant weight loss was documented in the control group compared with the three treatments (n ≥ 25 in each group, experiments were repeated at least three times).
(B) Endoscopic evaluation shows a significant improvement in colitis score on day 12 for all 3 treatments. In comparison with arginine, citrulline was more beneficial (n ≥ 25 in each group). Bottom: a representative image of the colon taken by colonoscopy.
(C) A representative plot showing a significant reduction in colon length in the control group compared with the treated colons (n ≥ 15 in each group).
(D) The histological score for colitis was significantly lower in the treated colons compared with controls.
(E) Immunohistochemistry staining of colons for ASL shows higher expression after citrulline treatment compared with other treatments.
(F) FACS analysis showing that citrulline treatment is more effective than arginine in inducing NO synthesis in enterocytes.
(G) Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showing increased apoptosis in control colons compared with colons taken from mice treated with citrulline. Bottom: a quantification graph generated using Image-Pro Pulse software.
Error bars represent SEM.