Curative effects of fucoidan on acetic acid induced ulcerative colitis in rats via modulating aryl hydrocarbon receptor and phosphodiesterase-4

Bagalagel, Alaa; Diri, Reem; Noor, Adeeb; Almasri, Deina; Bakhsh, Hussain T.; Kutbi, Hussam Ibrahim; Al‐Gayyar, Mohammed M.H.

doi:10.1186/s12906-022-03680-4

Cited by 21 publications

(10 citation statements)

References 40 publications

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“…In addition, inhibition of Nrf2 significantly enhanced the erastin- and sorafenib-induced suppression of HCC [ 25 ]. One of the downstream of Nrf-2 is HO-1, which is one of the antioxidant defense proteins [ 26 , 27 ]. HO-1 overexpression participates in the pathogenesis and progression of some malignancies.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Anticancer Activity of Blocking TNF Type 1 Receptors in Thioacetamide-Induced Hepatocellular Carcinoma in a Rat Model

Bagalagel¹,

Diri²,

Noor³

et al. 2022

Cureus

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Background Hepatocellular carcinoma (HCC) can explicate about 90% of the total primary liver cancer cases, with approximately 800,000 new cases identified each year worldwide. In addition, any changes in the expression of the tumor necrosis factor α (TNF-α) type 1 receptor (TNFR1) might impact many biological processes, which may lead to cancer. Aims We conducted the following study to investigate the ability of CAY10500, a TNF-α inhibitor that prevents binding to the TNF receptor 1, to produce anticancer effects against hepatocellular carcinoma experimentally induced in rats and to discover its effect on nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Materials and methods HCC was induced in rats via 200 mg/kg thioacetamide followed by treating some rats with IV 1 mg/kg CAY10500. Assessment of the liver impairment was by measuring the serum α-fetoprotein (AFP) and investigation of liver sections stained with hematoxylin/eosin. The hepatic expression of both the messenger RNA (mRNA) and protein levels of TNF-α, TNFR1, Nrf2, and HO-1 was assessed. Results We found that CAY10500 increased the survival percent of rats associated with a reduction in serum AFP and the number of hepatic nodules. Besides, CAY10500 reduced the expression of TNFR1 without affecting the expression of TNF-α. Finally, CAY10500 increased the expression of both Nrf2 and HO-1. Conclusions Inhibition of TNFR1 expression in HCC by using CAY10500 produced therapeutic effects as indicated by increasing the survival rate, reducing the serum AFP level, decreasing liver nodules, and improving hepatocytes’ structure. In addition, TNFR1 significantly enhanced the expression of Nrf2 and HO-1.

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Section: Discussionmentioning

confidence: 99%

Evaluating the Anticancer Activity of Blocking TNF Type 1 Receptors in Thioacetamide-Induced Hepatocellular Carcinoma in a Rat Model

Bagalagel¹,

Diri²,

Noor³

et al. 2022

Cureus

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“…To observe intestinal morphology, we performed H&E staining according to previous method 38 . In brief, colonic tissues were fixed with 4% paraformaldehyde, dehydrated by gradient concentration ethanol (75%, 85%, 100%), embedded in paraffin, sectioned (4 μm), and stained with hematoxylin and eosin for pathological observation.…”

Section: Methodsmentioning

confidence: 99%

Lidocaine ameliorates intestinal barrier dysfunction in irritable bowel syndrome by modulating corticotropin‐releasing hormone receptor 2

Wang,

Qiao,

Yao

et al. 2023

Neurogastroenterology Motil

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BackgroundIntestinal barrier dysfunction is a prevalent pathogenic factor underlying various disorders. Currently there is no effective resolution. Previous studies have reported the potential anti‐inflammatory properties of lidocaine and its ability to alleviate visceral hypersensitivity in individuals with irritable bowel syndrome (IBS). Therefore, our study will further verify the effect of lidocaine on intestinal barrier dysfunction in IBS and investigate the underlying mechanisms.MethodsIn this study, we investigated the role of lidocaine by assessing visceral hypersensitivity, body weight, inflammatory factors, fluorescein isothiocyanate‐dextran 4000 (FD4) flux, tight junctions (TJs) and spleen and thymus index in rats subjected to water avoidance stress (WAS) to mimic intestinal barrier dysfunction in IBS with and without lidocaine. In vitro, we investigated the role of corticotropin‐releasing hormone receptor 2 (CRHR2) in lidocaine‐treated Caco2 cells using small interfering RNA (siRNA) targeting CRHR2.Key ResultsIn WAS rats, lidocaine significantly restored weight loss, damaged TJs, spleen index and thymus index and inhibited abdominal hypersensitivity as well as blood levels of markers indicating intestinal permeability, such as diamine oxidase (DAO), D‐lactic acid (D‐Lac) and lipopolysaccharide (LPS). Consequently, the leakage of FD4 flux from intestine was significantly attenuated in lidocaine group, and levels of intestinal inflammatory factors (IL‐1β, IFN‐γ, TNF‐α) were reduced. Interestingly, lidocaine significantly suppressed corticotropin‐releasing hormone (CRH) levels in lamina propria cells, while the CRH receptor CRHR2 was upregulated in intestinal epithelial cells. In vitro, lidocaine enhanced the expression of CRHR2 on Caco‐2 intestinal epithelial cells and restored disrupted TJs and the epithelial barrier caused by LPS. Conversely, these effects were diminished by a CRHR2 antagonist and siRNA‐CRHR2, suggesting that the protective effect of lidocaine depends on CRHR2.Conclusions and InferencesLidocaine ameliorates intestinal barrier dysfunction in IBS by potentially modulating the expression of CRHR2 on intestinal epithelial cells.

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“…Rats were lightly anaesthetized with ether and received a single intracolonic administration of 2 ml of 4% acetic acid using a soft paediatric lubricated catheter. Rats were maintained in a horizontal position for 2 min to prevent drainage of acetic acid 16,17 …”

Section: Methodsmentioning

confidence: 99%

The therapeutic effects of cycloastragenol in ulcerative colitis by modulating SphK/MIP‐1α/miR‐143 signalling

Bagalagel

Diri

Noor

et al. 2022

Basic Clin Pharma Tox

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Patients with ulcerative colitis (UC) experience diarrhoea, hematochezia and abdominal pain. UC is a well-known health challenge affecting 200-250 per 100 000 individuals worldwide, with a similar prevalence in both sexes and elevated upon activation of gut immune responses. We evaluated the potential therapeutic effects of cycloastragenol in experimentally induced UC rats and examined the modulation of sphingosine kinase (SphK), macrophage inflammatory protein (MIP)-1α and miR-143. We treated UC rats with 30 mg/kg cycloastragenol and assessed gene and protein expression levels of SphK, MIP-1α, B-cell lymphoma 2 (BCL2), BCL2-associated X (BAX), miR-143, NF-κB, tumour necrosis factor (TNF)-α and active caspase-3. Colon sections were examined using electron microscopy; additional sections were stained with haematoxylin-eosin or immunostained with anti-TNF-α and anti-caspase-3 antibodies. Electron microscopy of UC specimens revealed dark distorted goblet cell nuclei with disarranged mucus granules and a nondistinct brush border with atypical microvilli. Haematoxylin-eosin staining showed damaged intestinal glands, severe haemorrhage and inflammatory cell infiltration. Cycloastragenol treatment improved the induced morphological changes. In UC rats, cycloastragenol significantly reduced expression levels of SphK, MIP-1α, BAX, NF-κB, TNF-α and active caspase-3, associated with BCL2 and miR-143 overexpression. Therefore, cycloastragenol protects against UC by modulating SphK/MIP-1α/miR-143, subsequently deactivating inflammatory and apoptotic pathways.K E Y W O R D S active caspase-3, B-cell lymphoma 2 (BCL2), BCL2 associated X (BAX), macrophage inflammatory protein (MIP)-1α, miR-143, nuclear factor (NF)κB, sphingosine kinase (SphK), tumour necrosis factor (TNF)-α

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Curative effects of fucoidan on acetic acid induced ulcerative colitis in rats via modulating aryl hydrocarbon receptor and phosphodiesterase-4

Cited by 21 publications

References 40 publications

Evaluating the Anticancer Activity of Blocking TNF Type 1 Receptors in Thioacetamide-Induced Hepatocellular Carcinoma in a Rat Model

Evaluating the Anticancer Activity of Blocking TNF Type 1 Receptors in Thioacetamide-Induced Hepatocellular Carcinoma in a Rat Model

Lidocaine ameliorates intestinal barrier dysfunction in irritable bowel syndrome by modulating corticotropin‐releasing hormone receptor 2

The therapeutic effects of cycloastragenol in ulcerative colitis by modulating SphK/MIP‐1α/miR‐143 signalling

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