Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway

Liver cirrhosis affects the structures and physiological functions of the intestine. Our previous study revealed that liver injury inhibited 25-hydroxylation of vitamin D (25(OH)-VD). The aim of this study was to investigate the roles and mechanisms of vitamin D in liver cirrhosis-induced intestinal...

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Main Authors: Luo Mei, Xu Yuanhong, Li Jike, Luo Dongxia, Zhu Li, Wu Yanxi, Liu Xiaodong, Wu Pengfei
Format: Article
Language:English
Published: De Gruyter 2023-05-01
Series:Open Medicine
Subjects:
Online Access:https://doi.org/10.1515/med-2023-0714
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author Luo Mei
Xu Yuanhong
Li Jike
Luo Dongxia
Zhu Li
Wu Yanxi
Liu Xiaodong
Wu Pengfei
author_facet Luo Mei
Xu Yuanhong
Li Jike
Luo Dongxia
Zhu Li
Wu Yanxi
Liu Xiaodong
Wu Pengfei
author_sort Luo Mei
collection DOAJ
description Liver cirrhosis affects the structures and physiological functions of the intestine. Our previous study revealed that liver injury inhibited 25-hydroxylation of vitamin D (25(OH)-VD). The aim of this study was to investigate the roles and mechanisms of vitamin D in liver cirrhosis-induced intestinal injury. The rat liver cirrhosis model was established through the administration of carbon tetrachloride (CCl4) for 8 weeks. Hematoxylin–eosin staining was performed to unveil the intestinal injury induced by liver cirrhosis. Enzyme-linked immunosorbent and reverse transcription PCR (RT-PCR) analysis were used to determine the levels of 25(OH)-VD, vitamin D receptor, Cytochrome P450 24A1 (CYP24A1), and α-defensin 5 (DEFA5) in rat and human serum of liver cirrhosis. Furthermore, liver cirrhosis rats were treated with low-dose (500 IU/kg) and high-dose (2,000 IU/kg) vitamin D intraperitoneally. The expression levels of TLR4/MyD88/NF-κB signaling pathway were evaluated by RT-PCR and Western blot. In conclusion, we determined the deficiency of vitamin D and down-regulation of DEFA5 and intestinal damage induced by liver cirrhosis. Moreover, vitamin D effectively inhibited liver cirrhosis-induced intestinal inflammation and oxidative stress through the TLR4/MyD88/NF-κB pathway. Vitamin D might be a promising therapeutic strategy for future treatment of liver-induced intestinal injury.
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spelling doaj.art-8439f1800bab40da94edc35704ed07a62023-06-05T09:17:37ZengDe GruyterOpen Medicine2391-54632023-05-0118120697910.1515/med-2023-0714Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathwayLuo Mei0Xu Yuanhong1Li Jike2Luo Dongxia3Zhu Li4Wu Yanxi5Liu Xiaodong6Wu Pengfei7Infectious Disease Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, ChinaClinical Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, ChinaInfectious Disease Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, ChinaInfectious Disease Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, ChinaHepatology Clinic, Chengdu Public Health Clinical Center, Chengdu, 610061, ChinaInfectious Disease Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, ChinaClinical Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, ChinaInfectious Disease Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, ChinaLiver cirrhosis affects the structures and physiological functions of the intestine. Our previous study revealed that liver injury inhibited 25-hydroxylation of vitamin D (25(OH)-VD). The aim of this study was to investigate the roles and mechanisms of vitamin D in liver cirrhosis-induced intestinal injury. The rat liver cirrhosis model was established through the administration of carbon tetrachloride (CCl4) for 8 weeks. Hematoxylin–eosin staining was performed to unveil the intestinal injury induced by liver cirrhosis. Enzyme-linked immunosorbent and reverse transcription PCR (RT-PCR) analysis were used to determine the levels of 25(OH)-VD, vitamin D receptor, Cytochrome P450 24A1 (CYP24A1), and α-defensin 5 (DEFA5) in rat and human serum of liver cirrhosis. Furthermore, liver cirrhosis rats were treated with low-dose (500 IU/kg) and high-dose (2,000 IU/kg) vitamin D intraperitoneally. The expression levels of TLR4/MyD88/NF-κB signaling pathway were evaluated by RT-PCR and Western blot. In conclusion, we determined the deficiency of vitamin D and down-regulation of DEFA5 and intestinal damage induced by liver cirrhosis. Moreover, vitamin D effectively inhibited liver cirrhosis-induced intestinal inflammation and oxidative stress through the TLR4/MyD88/NF-κB pathway. Vitamin D might be a promising therapeutic strategy for future treatment of liver-induced intestinal injury.https://doi.org/10.1515/med-2023-0714liver cirrhosisvitamin dintestinal injuryα-defensin 5oxidative stress
spellingShingle Luo Mei
Xu Yuanhong
Li Jike
Luo Dongxia
Zhu Li
Wu Yanxi
Liu Xiaodong
Wu Pengfei
Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
Open Medicine
liver cirrhosis
vitamin d
intestinal injury
α-defensin 5
oxidative stress
title Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
title_full Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
title_fullStr Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
title_full_unstemmed Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
title_short Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
title_sort vitamin d protects intestines from liver cirrhosis induced inflammation and oxidative stress by inhibiting the tlr4 myd88 nf κb signaling pathway
topic liver cirrhosis
vitamin d
intestinal injury
α-defensin 5
oxidative stress
url https://doi.org/10.1515/med-2023-0714
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