Betaine Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats via Inhibiting Inflammatory Response

Yang, Jiamei; Zhou, Ran; Zhang, Min; H, Tan; Yu, Jian‐Qiang

doi:10.3390/molecules23061274

Cited by 49 publications

(41 citation statements)

References 59 publications

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“…Because of the hydrophobicity of the 3 methyl groups and hydrophilicity of the carboxyl, a tight protective membrane could be formed around cells to prevent from oxidative stress and cell damage . The results are in line with previous findings that betaine prevents oxidative stress, inhibits apoptosis, and possesses antiinflammatory effects …”

Section: Discussionsupporting

confidence: 91%

Role of betaine in liver injury induced by the exposure to ionizing radiation

Shedid

Abdel‐Magied

Saada

2018

Environmental Toxicology

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Oxidative stress, apoptosis, and fibrosis may play a major role in the development of radiationinduced liver damage. Betaine, a native compound widely present in beetroot, was reported to possess hepato-protective properties. The objective of this study was to investigate the influence of betaine on radiation-induced liver damage. Animals were exposed to 9 Gy applied in 3 doses of 3 Gy/wk. Betaine (400 mg/kg/d), was orally supplemented to rats after the first radiation dose, and daily during the irradiation period. Animals were sacrificed 1 day after the last dose of radiation. The results showed that irradiation has induced oxidative stress in the liver denoted by a significant elevation in malondialdehyde, protein carbonyl, and 8-hydroxy-2-deoxyguanosine with a significant reduction in catalase activity and glutathione (GSH) content. The activity of the detoxification enzyme cytochrome P450 (CYP450) increased while GSH transferase (GSH-T) decreased. The activity of the apoptotic marker caspase-3 increased concomitant with increased hyaluronic acid, hydroxyproline, laminin (LN), and collagen IV. These alterations were associated with a significant increase of gamma-glutamyl transferase, alkaline phosphatase and alanine and aspartate aminotransferase markers of liver dysfunction. Betaine treatment has significantly attenuated oxidative stress, decreased the activity of CYP450, enhanced GSH-T, reduced the activity of caspase-3, and the level of fibrotic markers concomitant with a significant improvement of liver function. In conclusion, betaine through its antioxidant activity and by enhancing liver detoxification and reducing apoptosis may alleviate the progression of liver fibrosis and exert a beneficial impact on radiation-induced liver damage.

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Section: Discussionsupporting

confidence: 91%

Role of betaine in liver injury induced by the exposure to ionizing radiation

Shedid

Abdel‐Magied

Saada

2018

Environmental Toxicology

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“…Zhao et al reported that the NF‐κB pathway may contribute to candesartan‐induced initiation and progression of PIH 36 . Furthermore, betaine treatment has been shown to attenuate pulmonary arterial hypertension through the inhibition of inflammatory response by inactivating the NF‐κB pathway 37 . Impairment of ET‐1 by suppression of ETAR deactivates the NF‐κB pathway, supporting the implication of mediation of the ET‐1 axis in neuropathic pain 38 .…”

Section: Discussionmentioning

confidence: 93%

Long noncoding RNA MALAT1 contributes to pregnancy‐induced hypertension development by enhancing oxidative stress and inflammation through the regulation of the miR‐150‐5p/ET‐1 axis

Zhao

et al. 2020

FASEB j.

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Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified previously in the pathogenesis of hypertension and some gestational diseases. However, the biological functions of MALAT1 in pregnancy-induced hypertension (PIH) are still poorly understood. Herein, we aim to explore the functional relevance of MALAT1 in PIH and to explain the potential underlying mechanisms. We found that the levels of ET-1 and MALAT1 were upregulated and that of miR-150-5p were downregulated in the serum of pregnant women with PIH and the aortic endothelial cells (ECs) of reduced uterine perfusion pressure (RUPP)-induced rat models. In aortic ECs, MALAT1 could competitively bind to miR-150-5p to upregulate the expression of ET-1. The MALAT1/ miR-150-5p/ET-1 axis regulated the expression of endothelin B receptor (ETBR) in aortic ECs leading to oxidative stress imbalance and increased the release of proinflammatory cytokines (IL-18 and IL-1β), which concurrently activated the NF-κB pathway to regulate the ETBR expression and to stimulate smooth muscle cell (SMC) contraction. Furthermore, silencing MALAT1 could alleviate the hypertensive symptoms of RUPP-induced rat models. Taken conjointly, the upregulation of MALAT1 can reduce the expression of ET-1 by competitively binding to miR-150-5p, which enhances the expression of ETBR via the activation of the NF-κB pathway in SMCs, thus exacerbating the hypertensive symptoms in the RUPP-induced rat models. K E Y W O R D Sendothelial cells, endothelin-1, metastasis-associated lung adenocarcinoma transcript 1, microRNA-150-5p, NF-κB pathway, pregnancy-induced hypertension, smooth muscle cells

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“…There are lots of credibility evidences show that betaine also have the function of anti-inflammation and improving intestinal barrier function [23] . Yang et al found that betaine alleviates monocrotaline-induced pulmonary hypertension in rat by restraining the inflammatory response, such as down-regulating the NF-κB signaling pathway or inhibiting the inflammatory reaction [24] . Olli.…”

Section: Discussionmentioning

confidence: 99%

Betaine attenuates LPS-induced downregulation of Occludin and Claudin-1 and restores intestinal barrier function

et al. 2019

Preprint

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Background: The intestinal epithelial barrier, which works as the first line of defense between the intestinal environment and the parasitifer, once destroyed, it will cause serious inflammation or other intestinal diseases. Tight junctions (TJs) play a vital role to maintain the integrity of the epithelial barrier. Lipopolysaccharide (LPS), one of the most important inflammatory factors will downregulate specific TJ proteins including Occludin and Claudin-1 and impair integrity of the epithelial barrier. Betaine (Bet) has excellent anti-inflammatory activity but whether Bet has any effect on tight junction proteins, particularly on LPS-induced dysfunction of epithelial barriers remains unknown. Intestinal porcine epithelial cells (IPEC-J2) were used as an in vitro model, the purpose of this study is to explore the pharmacological effect of Bet on improving intestinal barrier function represented by TJ proteins.Results: The results demonstrated that Bet enhanced the expression of tight junction proteins while LPS（ 1μg /m L）downregulates the expression of these proteins. Furthermore, Bet attenuates LPS-induced decreases of tight junction proteins both shown by WB and RT-PCR. The immunofluorescent images consistently revealed that LPS induced the disruption of tight junction protein Claudin-1 and reduced its expression while Bet could reverse these alterations. Similar protective role of Bet on intestinal barrier function was observed by transepithelial electrical resistance (TEER) approach. Conclusion: In conclusion, our research demonstrated that Bet attenuated LPS-induced downregulation of Occludin and Claudin-1 and restored the intestinal barrier function.

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Betaine Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats via Inhibiting Inflammatory Response

Cited by 49 publications

References 59 publications

Role of betaine in liver injury induced by the exposure to ionizing radiation

Role of betaine in liver injury induced by the exposure to ionizing radiation

Long noncoding RNA MALAT1 contributes to pregnancy‐induced hypertension development by enhancing oxidative stress and inflammation through the regulation of the miR‐150‐5p/ET‐1 axis

Betaine attenuates LPS-induced downregulation of Occludin and Claudin-1 and restores intestinal barrier function

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