Cyclooxygenase-2 activates EGFR–ERK1/2 pathway via PGE2-mediated ADAM-17 signaling in testosterone-induced benign prostatic hyperplasia

Fetoh, Mohammed E Abo-El; Abdel-Fattah, Maha M.; Mohamed, Wafaa R.; Ramadan, Laila A.; Afify, Hassan

doi:10.1007/s10787-022-01123-7

Cited by 4 publications

(3 citation statements)

References 75 publications

(121 reference statements)

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“…TP administration used to build the BPH model in rats was previously proven to generate excessive production of ROS together with attenuation of cellular antioxidant mechanisms [14,42,43]. This could justify the increase in oxidant MDA enzyme and the significantly regressed levels of antioxidant GSH and SOD enzymes in prostatic tissue versus the control group in the current study.…”

Section: Plos Onementioning

confidence: 70%

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Diacerein provokes apoptosis, improves redox balance, and downregulates PCNA and TNF-α in a rat model of testosterone-induced benign prostatic hyperplasia: A new non-invasive approach

Rasheed,

Sadek,

Khattab

et al. 2023

PLoS ONE

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One of the most prevalent chronic conditions affecting older men is benign prostatic hyperplasia (BPH), causing severe annoyance and embarrassment to patients. The pathogenesis of BPH has been connected to epithelial proliferation, inflammation, deranged redox balance, and apoptosis. Diacerein (DIA), the anthraquinone derivative, is a non-steroidal anti-inflammatory drug. This study intended to investigate the ameliorative effect of DIA on the prostatic histology in testosterone-induced BPH in rats. BPH was experimentally induced by daily subcutaneous injection of testosterone propionate for four weeks. The treated group received DIA daily for a further two weeks after induction of BPH. Rats’ body and prostate weights, serum-free testosterone, dihydrotestosterone, and PSA were evaluated. Prostatic tissue was processed for measuring redox balance and histopathological examination. The BPH group had increased body and prostate weights, serum testosterone, dihydrotestosterone, PSA, and oxidative stress. Histologically, there were marked acinar epithelial and stromal hyperplasia, inflammatory infiltrates, and increased collagen deposition. An immunohistochemical study showed an increase in the inflammatory TNF-α and the proliferative PCNA markers. Treatment with DIA markedly decreased the prostate weight and plasma hormones, improved tissue redox balance, repaired the histological changes, and increased the proapoptotic caspase 3 expression besides the substantial reduction in TNF-α and PCNA expression. In conclusion, our study underscored DIA’s potential to alleviate the prostatic hyperplastic and inflammatory changes in BPH through its antioxidant, anti-inflammatory, antiproliferative, and apoptosis-inducing effects, rendering it an effective, innovative treatment for BPH.

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Section: Plos Onementioning

confidence: 70%

“…These cytokines support the expansion of epithelial cells and enlargement of the prostate [12,13]. Certain inflammatory pathways can be activated by oxidative stress via activating transcription factors like NF-кB, which in turn regulate the gene expression of proinflammatory mediators, including TNF-α [14].…”

Section: Introductionmentioning

confidence: 99%

Diacerein provokes apoptosis, improves redox balance, and downregulates PCNA and TNF-α in a rat model of testosterone-induced benign prostatic hyperplasia: A new non-invasive approach

Rasheed,

Sadek,

Khattab

et al. 2023

PLoS ONE

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“…The median of the RNA expression was calculated and used as a threshold to differentiate between the higher and lower expression within the factor groups. The mRNA expression was normalized to the expression of the house keeping gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH) 60 , 61 .…”

Section: Methodsmentioning

confidence: 99%

Ubiquinol attenuates γ-radiation induced coronary and aortic changes via PDGF/p38 MAPK/ICAM-1 related pathway

El-Sabbagh,

Fadel,

El-Hazek

et al. 2023

Sci Rep

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Endothelial vascular injury is one of the most pivotal disorders emerging during radiotherapy. It is crucial to rely on strong antioxidants to defend against vascular damage. The current study was carried out to investigate the ameliorative effect of ubiquinol (Ubq) against gamma (γ)-radiation induced aortic and coronary changes, with highlighting its role in suppression of p38 mitogen activated protein kinase (MAPK). Exposure to γ-radiation was adopted as a potent detrimental model that induces vascular tissue damage. Concisely, male albino rats were irradiated at a dose level of 7 Gy and treated daily with Ubq (10 mg/kg/day, p.o.) for 7 days pre-and post-irradiation. At the end of the experiment, lipid profile, 8-hydroxydeoxyguanosine (8-OHdG), gene expression of intercellular adhesion molecule (ICAM-1), platelet derived growth factor (PDGF), p38 MAPK and matrix metalloproteinase-9 (MMP-9) were estimated. Exposure to radiation significantly deteriorates aortic and coronary tissues. Conversely, administration of Ubq significantly reduced serum t-cholesterol, LDL and triglycerides (p = 0.001). In addition, Ubq prevented oxidative DNA damage (8-OHdG) (p = 0.1) and reduced serum MMP-9 (p = 0.001) which contributed to the endothelial cells damage. The positive impact of Ubq was more apparent in suppression of both PDGF (p = 0.001) and p38 MAPK (p = 0.1) protein concentrations, leading subsequently in reduction of ICAM-1 (p = 0.001) gene expression. As a conclusion, vascular endothelial damage brought on by γ-radiation is one of the leading causes of coronary and aortic deteriorations which could be successfully mitigated by Ubq.

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The Causal Relationship between Chronic Obstructive Pulmonary Disease and Cardiovascular Diseases: Role of Systemic Inflammation and NF-κB/COX-2 Pathway

Wu,

Zhang,

et al. 2023

Preprint

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Background Chronic Obstructive Pulmonary Disease (COPD) is a significant global health issue that often coexists with cardiovascular and cerebrovascular diseases. The aim of this study is to investigate the causal relationship between COPD and these diseases, with a focus on the role of systemic inflammation and the NF-κB/COX-2 pathway. Methods The Two-Sample Mendelian Randomization (TSMR) approach was used to analyze the genetic correlation between COPD and the risks of ischemic stroke (IS) and acute myocardial infarction (AMI) using data from several large biobanks. In addition, in vivo experiments with ApoE knockout mice and in vitro assays with primary mouse aorta endothelial cells were conducted to explore the role of the NF-κB/COX-2 pathway in COPD-related systemic inflammation. Results The MR analysis revealed a significant association between COPD and increased risks of IS (OR: 1.152) and AMI (OR: 1.001). In vivo findings showed exacerbated pulmonary dysfunction and atherogenesis in mice with both COPD and high-fat diet (HFD), with notable histological changes in lung and aortic tissues. Inflammatory markers and lipid profiles were significantly altered in these models. In vitro studies demonstrated that COPD-induced systemic inflammation impaired endothelial cell function. These changes were mitigated by inhibiting the NF-κB/COX-2 pathway. Conclusions This study provides strong evidence of a causal link between COPD and an elevated risk of cardiovascular diseases, mediated by systemic inflammation and the NF-κB/COX-2 pathway. These findings highlight the importance of addressing cardiovascular risks in COPD management and suggest that the NF-κB/COX-2 pathway could be a potential therapeutic target for reducing comorbid cardiovascular conditions in COPD patients.

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Cyclooxygenase-2 activates EGFR–ERK1/2 pathway via PGE2-mediated ADAM-17 signaling in testosterone-induced benign prostatic hyperplasia

Cited by 4 publications

References 75 publications

Diacerein provokes apoptosis, improves redox balance, and downregulates PCNA and TNF-α in a rat model of testosterone-induced benign prostatic hyperplasia: A new non-invasive approach

Diacerein provokes apoptosis, improves redox balance, and downregulates PCNA and TNF-α in a rat model of testosterone-induced benign prostatic hyperplasia: A new non-invasive approach

Ubiquinol attenuates γ-radiation induced coronary and aortic changes via PDGF/p38 MAPK/ICAM-1 related pathway

The Causal Relationship between Chronic Obstructive Pulmonary Disease and Cardiovascular Diseases: Role of Systemic Inflammation and NF-κB/COX-2 Pathway

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