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Protective effect of 1,25-dihydroxyvitamin D3 on ethanol-induced intestinal barrier injury both in vitro and in vivo
- Source :
- Toxicology letters. 237(2)
- Publication Year :
- 2015
-
Abstract
- Studies have suggested the role of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in protecting intestinal barrier function from injuries induced by multiple reagents. Vitamin D deficiency was reported to be associated with poor prognosis in patients with alcoholic liver disease (ALD). This study is designed to investigate the effect of 1,25(OH)2D3 on ethanol-induced intestinal barrier dysfunction and the underlying mechanisms utilizing Caco-2 cell monolayers and a mouse model with acute ethanol injury. In Caco-2 monolayers, ethanol significantly increased monolayer permeability, disrupted TJ distribution, increased phosphorylation level of MLC, and induced generation of ROS compared with controls. However, pre-treatment with 1,25(OH)2D3 greatly ameliorated the ethanol-induced barrier dysfunction, TJ disruption, phosphorylation level of MLC, and generation of ROS compared with ethanol-exposed monolayers. Mice fed with vitamin d-sufficient diet had a higher plasma level of 25(OH)D3 and were more resistant to ethanol-induced acute intestinal barrier injury compared with the vitamin d-deficient group. These results suggest that the suppression of generation of ROS and increased phosphorylation level of MLC might be one of the mechanisms underlying the protective effect of 1,25(OH)2D3 on ethanol-induced intestinal barrier injury and provide evidence for the application of vitamin D as therapeutic factors against ethanol-induced gut leakiness.
- Subjects :
- Vitamin
medicine.medical_specialty
Myosin Light Chains
Cell Survival
Toxicology
Protective Agents
Calcitriol receptor
vitamin D deficiency
Permeability
chemistry.chemical_compound
Mice
Calcitriol
In vivo
Internal medicine
medicine
Vitamin D and neurology
Electric Impedance
Animals
Humans
Intestinal Mucosa
Phosphorylation
Barrier function
Tight junction
Ethanol
General Medicine
medicine.disease
Mice, Inbred C57BL
Endocrinology
chemistry
Immunology
Zonula Occludens-1 Protein
Female
Caco-2 Cells
Subjects
Details
- ISSN :
- 18793169
- Volume :
- 237
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Toxicology letters
- Accession number :
- edsair.doi.dedup.....de9618b6479cd2fdea01ebf00dbfb40f