High dose lithium chloride causes colitis through activating F4/80 positive macrophages and inhibiting expression of Pigr and Claudin-15 in the colon of mice.

Abstract

OBJECTIVE:

Lithium chloride (LiCl) was a mood stabilizer for bipolar affective disorders and it could activate Wnt/β-catenin signaling pathway both in vivo and in vitro. Colon is one of a very susceptible tissues to Wnt signaling pathway, and so it would be very essential to explore the toxic effect of a high dose of LiCl on colon.

METHODS:

C57BL/6 mice were injected intraperitoneally with 200 mg/kg LiCl one dose a day for 5 days to activate Wnt signal pathway in intestines. H&E staining was used to assess the colonic tissues of mice treated with high dose of LiCl. The expression of inflammation-associated genes and tight junction-associated genes in colons was measured using qPCR, Western blot and immunostaining methods. The gut microbiome was tested through 16S rDNA gene analysis.

RESULTS:

The differentiation of enteroendocrine cells in colon was inhibited by treatment of 200 mg/kg LiCl. The F4/80 positive macrophages in colon were activated by high dose of LiCl, and migrated from the submucosa to the lamina propria. The expression of pro-inflammatory genes TNFα and IL-1β was increased in the colon of high dose of LiCl treated mice. Clostridium_sp_k4410MGS_306 and Prevotellaceae_UCG_001 were specific and predominant for the high dose of LiCl treated mice. The expression of IgA coding genes, Pigr and Claudin-15 was significantly decreased in the colon tissues of the high dose of LiCl treated mice.

CONCLUSION:

200 mg/kg LiCl might cause the inflammation in colon of mice through activating F4/80 positive macrophages and inhibiting the expression of IgA coding genes in plasma cells and the expression of Pigr and Claudin-15 in colonic epithelial cells, providing evidences for the toxic effects of high dose of LiCl on colon.

• Authors: Zili Lei, Lanxiang Yang, Yuting Lei, Yanhong Yang, Xueying Zhang, Qi Song, Guibin Chen, Wanwan Liu, Huijuan Wu, Jiao Guo
• Journal: Toxicology (Toxicology) Vol. 457 Pg. 152799 (06 15 2021) ISSN: 1879-3185 [Electronic] Ireland
• PMID: 33901603 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Antimanic Agents
• Claudins
• Oscar protein, mouse
• Receptors, Cell Surface
• claudin 15
• Lithium Chloride

Topics

• Animals
• Antimanic Agents (administration & dosage, toxicity)
• Claudins (antagonists & inhibitors, biosynthesis)
• Colitis (chemically induced, metabolism, pathology)
• Colon (drug effects, metabolism, pathology)
• Dysbiosis (chemically induced, metabolism, pathology)
• Gene Expression
• Lithium Chloride (administration & dosage, toxicity)
• Macrophages (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Receptors, Cell Surface (antagonists & inhibitors, biosynthesis)
• Wnt Signaling Pathway (drug effects, physiology)