Zili Lei1, Lanxiang Yang2, Yuting Lei3, Yanhong Yang4, Xueying Zhang2, Qi Song3, Guibin Chen3, Wanwan Liu3, Huijuan Wu2, Jiao Guo5. 1. Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Disease, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China. Electronic address: 3182683090@qq.com. 2. Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Disease, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China. 3. Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Disease, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China. 4. The First Affiliated Hospital (School of Clinical Medicine), Guangdong Pharmaceutical University, Nong-Lin-Xia Road 19#, Yue-Xiu District, Guangzhou 510080, PR China. 5. Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Disease, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, 510006, PR China. Electronic address: gyguoyz@163.com.
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.
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.