Molecular mechanisms in the pathogenesis of N-nitrosodimethylamine induced hepatic fibrosis

George, Joseph; Tsuchishima, Mutsumi; Tsutsumi, Mikihiro

doi:10.1038/s41419-018-1272-8

Cited by 73 publications

(49 citation statements)

References 113 publications

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“…There are over 8000 compounds identified as carcinogens to date. Carcinogens can stimulate cancer via the production of critical pro-inflammatory, pro-angiogenic and pro-tumorigenic cytokines/transcription factors, including TNF-α, IL-6, and NF-κB, as well as proto-oncogenes (e.g., c-Myc) ( Chen, Yan, & Ye, 1998 ; George, Tsuchishima, & Tsutsumi, 2019 ). Moreover, carcinogens may impair the host protective immune response via immunotoxicity, including increased apoptosis of leukocytes and reactive oxygen species ( Iwaniuk, Jablonska, Jablonski, Ratajczak-Wrona, & Garley, 2015 ; Jablonski, Jablonska, & Chojnowski, 2001 ; Jablonski, Jablonska, & Leonik, 2011 ; Nowak, Ratajczak-Wrona, Garley, & Jablonska, 2018 ; Ratajczak-Wrona et al, 2014 ).…”

Section: Carcinogens and Inflammationmentioning

confidence: 99%

“…In addition, NDMA increases gut permeability, which accelerates the entry of LPS into the blood stream. Activated Kupffer cells then produce several cytokines and growth factors such as TNF-α, TGF-β1, PDGF, and IL−1β ( George, Tsuchishima, & Tsutsumi, 2019 ). These signaling molecules drive chronic inflammation with continued carcinogen exposure as the pro-inflammatory cytokines such as IL-1β, IL-6, IL-22, IFN-γ, and TNF-α further activate NF-κB and TGF-β generating a feedforward pro-tumorigenic inflammatory cycle ( George, Tsuchishima, & Tsutsumi, 2019 ).…”

Section: Mechanisms Of Pro-tumorigenic Activity By Carcinogensmentioning

confidence: 99%

“…Activated Kupffer cells then produce several cytokines and growth factors such as TNF-α, TGF-β1, PDGF, and IL−1β ( George, Tsuchishima, & Tsutsumi, 2019 ). These signaling molecules drive chronic inflammation with continued carcinogen exposure as the pro-inflammatory cytokines such as IL-1β, IL-6, IL-22, IFN-γ, and TNF-α further activate NF-κB and TGF-β generating a feedforward pro-tumorigenic inflammatory cycle ( George, Tsuchishima, & Tsutsumi, 2019 ). Further, co-exposure to AFB 1 and FB 1 increase carcinogenicity via upregulation of IL-10, IL-4, lipid peroxidation (LP), and caspase 3 ( Abbes et al, 2016 ).…”

Section: Mechanisms Of Pro-tumorigenic Activity By Carcinogensmentioning

confidence: 99%

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Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

138

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Inflammation in the tumor microenvironment is a hallmark of cancer and is recognized as a key characteristic of carcinogens. However, the failure of resolution of inflammation in cancer is only recently being understood. Products of arachidonic acid and related fatty acid metabolism called eicosanoids, including prostaglandins, leukotrienes, lipoxins, and epoxyeicosanoids, critically regulate inflammation, as well as its resolution. The resolution of inflammation is now appreciated to be an active biochemical process regulated by endogenous specialized pro-resolving lipid autacoid mediators which combat infections and stimulate tissue repair/regeneration. Environmental and chemical human carcinogens, including aflatoxins, asbestos, nitrosamines, alcohol, and tobacco, induce tumor-promoting inflammation and can disrupt the resolution of inflammation contributing to a devastating global cancer burden. While mechanisms of carcinogenesis have focused on genotoxic activity to induce mutations, nongenotoxic mechanisms such as inflammation and oxidative stress promote genotoxicity, proliferation, and mutations. Moreover, carcinogens initiate oxidative stress to synergize with inflammation and DNA damage to fuel a vicious feedback loop of cell death, tissue damage, and carcinogenesis. In contrast, stimulation of resolution of inflammation may prevent carcinogenesis by clearance of cellular debris via macrophage phagocytosis and inhibition of an eicosanoid/cytokine storm of pro-inflammatory mediators. Controlling the host inflammatory response and its resolution in carcinogen-induced cancers will be critical to reducing carcinogen-induced morbidity and mortality. Here we review the recent evidence that stimulation of resolution of inflammation, including pro-resolution lipid mediators and soluble epoxide hydrolase inhibitors, may be a new chemopreventive approach to prevent carcinogen-induced cancer that should be evaluated in humans.

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Section: Carcinogens and Inflammationmentioning

confidence: 99%

Section: Mechanisms Of Pro-tumorigenic Activity By Carcinogensmentioning

confidence: 99%

Section: Mechanisms Of Pro-tumorigenic Activity By Carcinogensmentioning

confidence: 99%

See 1 more Smart Citation

Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

138

View full text Add to dashboard Cite

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“…Several pathways and mechanisms have been described to unravel molecular mechanisms involved in the pathogenesis of liver fibrosis [15,48,[158][159][160]. Elevated levels of circulating CTS potentially contribute to disease progression, such as in various chronic inflammatory conditions like obesity, hypertension, NASH, cardiovascular disease, and further stimulate the proinflammatory and profibrotic response [91][92][93]99,102,[161][162][163][164].…”

Section: Cardiotonic Steroids Mediated Na/k-atpase Signaling and Fibrmentioning

confidence: 99%

Elucidating Potential Profibrotic Mechanisms of Emerging Biomarkers for Early Prognosis of Hepatic Fibrosis

Zehra

Curry

Pillai

et al. 2020

IJMS

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Hepatic fibrosis has been associated with a series of pathophysiological processes causing excessive accumulation of extracellular matrix proteins. Several cellular processes and molecular mechanisms have been implicated in the diseased liver that augments fibrogenesis, fibrogenic cytokines and associated liver complications. Liver biopsy remains an essential diagnostic tool for histological evaluation of hepatic fibrosis to establish a prognosis. In addition to being invasive, this methodology presents with several limitations including poor cost-effectiveness, prolonged hospitalizations, and risks of peritoneal bleeding, while the clinical use of this method does not reveal underlying pathogenic mechanisms. Several alternate noninvasive diagnostic strategies have been developed, to determine the extent of hepatic fibrosis, including the use of direct and indirect biomarkers. Immediate diagnosis of hepatic fibrosis by noninvasive means would be more palatable than a biopsy and could assist clinicians in taking early interventions timely, avoiding fatal complications, and improving prognosis. Therefore, we sought to review some common biomarkers of liver fibrosis along with some emerging candidates, including the oxidative stress-mediated biomarkers, epigenetic and genetic markers, exosomes, and miRNAs that needs further evaluation and would have better sensitivity and specificity. We also aim to elucidate the potential role of cardiotonic steroids (CTS) and evaluate the pro-inflammatory and profibrotic effects of CTS in exacerbating hepatic fibrosis. By understanding the underlying pathogenic processes, the efficacy of these biomarkers could allow for early diagnosis and treatment of hepatic fibrosis in chronic liver diseases, once validated.

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“…http: //www.ijmp.jor.br v. 11, n. 1, January-February 2020ISSN: 2236-269X DOI: 10.14807/ijmp.v11i1.944 2010BUZEA et al, 2015;PETRESCU et al, 2015;PETRESCU, 2008;PETRESCU, 2009;ABDUL-RAZZAK et al, 2012;AJITH et al, 2009;ATASAYAR et al, 2009;AHMED et al, 2011;COVIC et al, 2007;WILLIS, 1953;WILLIS, 1954WILLIS, , 1957HA, 2010;EL-GENDY, 2009;ENSTROM, 2014;GEORGE et al, 2019;HANSEN, 2014;RATH, 1990;RATH, 2003;YILMAZ, 2006;RAVNSKOV, 2009;KUNUTSOR, 2016;HICKEY, 2007;CHOUDHURY;GREENE, 2018;CHOUDHURY, 2018).…”

Section: Independent Journal Of Management and Production (Ijmandp)mentioning

confidence: 99%

Some aspects related to the human body plant

Petrescu¹,

Petrescu²

2020

Ind. Jour. Manag. & Prod.

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The paper presents some important aspects related to the human liver, which is a real human body's plant, having essential roles in human life, especially in the preparation of the food necessary for the organism, in the production of the various essential substances necessary for the body and the basic chemical elements. At the same time, the human liver has the role of detoxifying the body, processing and eliminating toxic elements from ingested foods. The liver secretes various substances necessary for the human body. The more we keep this vital organ healthier, the more human body becomes free, healthier, younger and vigorous. The liver is probably the organ with the most diverse functions in the human body. After ingestion of food, they are processed along the digestive tract and degraded to nutrients that will reach all tissues and organs in the body. The liver is an annexe of the digestive tract with a very complex structure. The morphological unit of the liver is the liver lobe. It has a pyramid shape and a length of a few millimeters. The liver contains up to 100,000 lobules.

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Molecular mechanisms in the pathogenesis of N-nitrosodimethylamine induced hepatic fibrosis

Cited by 73 publications

References 113 publications

Carcinogenesis: Failure of resolution of inflammation?

Carcinogenesis: Failure of resolution of inflammation?

Elucidating Potential Profibrotic Mechanisms of Emerging Biomarkers for Early Prognosis of Hepatic Fibrosis

Some aspects related to the human body plant

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