QNZ alleviated hepatocellular carcinoma by targeting inflammatory pathways in a rat model

Al‐Gayyar, Mohammed M.H.; Alattar, Abdullah; Alshaman, Reem; Hamdan, Ahmed M.

doi:10.1016/j.cyto.2021.155710

Cited by 10 publications

(6 citation statements)

References 36 publications

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“…Moreover, inflammatory cytokines such as TNF-α are highly elevated in HCC patients [ 19 ]. We have previously shown that the inhibition of both TNF-α and NFκB significantly had therapeutic effects against HCC in rats [ 13 ]. Therefore, we used CAY10500, a TNFα inhibitor that prevents binding to TNFR1, in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…The gene expression of TNF-α, TNFR1, Nrf2, and HO-1 mRNA levels in rat liver lysate was performed as described previously by our group [13][14][15]. GAPDH was used as a housekeeping gene and internal reference control.…”

Section: Quantitative Real-time Polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

“…We have previously published research about using QNZ, an inhibitor of both TNF-α and NFκB, to treat experimentally induced HCC in rats. QNZ significantly reduced the expression of inflammation, oxidative stress, and fibrosis [ 13 ]. Therefore, the next step will be to evaluate the ability to block TNFR1 receptors in treating HCC.…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Quantitative Real-time Polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

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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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“…The gene expression of AhR, IL-22, PDE4, cAMP, Nrf2 and HO-1 mRNA in rat colon was performed as described previously by our group [ 20 , 21 ]. β-actin was used as a housekeeping gene and internal reference control.…”

Section: Methodsmentioning

confidence: 99%

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

Bagalagel

Diri

Noor

et al. 2022

BMC Complement Med Ther

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Background Ulcerative colitis (UC) is an inflammatory bowel disease. Fucoidan, sulfated polysaccharide of brown seaweed, demonstrates various pharmacological actions as anti-inflammatory, anti-tumor and anti-bacterial effects. Therefore, we opt to investigate the potential curative effects of fucoidan in experimentally induced UC in rats through modulating aryl hydrocarbon receptor (AhR), phosphodiesterase-4 (PDE4), nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme Oxygenase-1 (HO-1). Methods UC was induced in rats using intracolonic 2 ml of 4% acetic acid. Some rats were treated with 150 mg/kg fucoidan. Samples of colon were used to investigate gene and protein expression of AhR, PDE4, Nrf2, HO-1 and cyclic adenosine monophosphate (cAMP). Sections of colon were stained with hematoxylin/eosin, Alcian blue or immune-stained with anti-PDE4 antibodies. Results Investigation of hematoxylin/eosin stained micro-images of UC rats revealed damaged intestinal glands, severe hemorrhage and inflammatory cell infiltration, while sections stained with Alcian Blue revealed damaged and almost absent intestinal glands. UC results in elevated gene and protein expression of PDE4 associated with reduced gene and protein expression of AhR, IL-22, cAMP, Nrf2 and HO-1. Finally, UC increased the oxidative stress and reduced antioxidant activity in colon tissues. All morphological changes as well as gene and protein expressions were ameliorated by fucoidan. Conclusion Fucoidan could treat UC induced in rats. It restored the normal weight and length of colon associated with morphological improvement as found by examining sections stained with hematoxylin/eosin and Alcian Blue. The curative effects could be explained by enhancing antioxidant activity, reducing the expression of PDE4 and increasing the expression of AhR, IL-22 and cAMP.

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“…Gene expression levels of NFκB, B-cell lymphoma 2 (BCL2), BCL2 associated X (BAX), MIP-1α, SphK, miR-143, TNF-α and caspase-3 mRNA in rat colon lysates were determined as described previously. 19,20 β-actin was used as a housekeeping gene and an internal reference control. Gene-specific PCR primers used are listed in Table 1.…”

Section: Quantitative Real-time Polymerase Chain Reaction (Qpcr)mentioning

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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QNZ alleviated hepatocellular carcinoma by targeting inflammatory pathways in a rat model

Cited by 10 publications

References 36 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

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

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

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