Lithium induces intestinothrophic effects in the healthy colon, but does not ameliorate dextran sulfate sodium-induced colitis in mice

SummaryBackground & aimsUlcerative colitis is characterized by severe damage of the colon epithelium. Wnt-signaling is important for repair and regeneration of the intestinal epithelium. Lithium activates Wnt-signaling through inhibition of Glycogen Synthase Kinase 3β. Lithium induced prolonged remission in a patient with a bipolar disorder and ulcerative colitis, suggesting a therapeutic potential for ulcerative colitis.MethodsHere, we investigated the effect of lithium (4 mg/day via a subcutaneous osmotic pump) on 5% dextran sulfate sodium-induced colitis in female Balb/c mice.ResultsAt day 7, colon length was significantly increased in lithium-treated compared to untreated mice (8.6 cm [7.0–9.5] versus 7.6 cm [6.7–8.0], p < 0.05). As expected, dextran sulfate sodium treatment reduced colon length (5.9 cm [5.1–6.5], p < 0.001), but this was not altered by lithium (6.0 cm [5.5–7.0]). No significant differences were detected in bodyweight, histology, inflammatory (myeloperoxidase, iNOS, cytokines) and Wnt-pathway (β-catenin, p-Glycogen Synthase Kinase 3β) markers between dextran sulfate sodium- and lithium/dextran sulfate sodium-treated mice.ConclusionsLithium has no therapeutic effect on dextran sulfate sodium-induced colitis in mice. However, in the healthy intestine it shows intestinothrophic potential that might be beneficial for short bowel patients.