Lack of nrf2 results in progression of proliferative lesions to neoplasms induced by long-term exposure to non-genotoxic hepatocarcinogens involving oxidative stress

Tasaki, Masayuki; Kuroiwa, Yoshihiro; Inoue, Tomoki; Hibi, Daisuke; Matsushita, Kohei; Kijima, Aki; Maruyama, Soichi; Nishikawa, Akiyoshi; Umemura, Takashi

doi:10.1016/j.etp.2013.07.003

Cited by 19 publications

(24 citation statements)

References 50 publications

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“…Therefore, the variation on antioxidant gene expressions is a result of DNA damage and the alteration of cellular key processes which might not be directly related, as mentioned before, to antioxidant cell defense. The key role of ROS on the initiation stage of carcinogenesis, causing DNA damage, and interference to repair damaged DNA is indubitably recognized (Marra et al, 2011;Tasaki et al, 2014). Biochemical data concerning antioxidant biomarkers should provide early results before any cell or histology significant changes.…”

Section: Discussionmentioning

confidence: 99%

“…ROS may interact and induce damage at different levels (cellular protein, lipids and DNA), causing cell malfunction. Oxidative stress is widely accepted as a major cancer cause, playing a key role in hepatocarcinogenesis, at both the initiation and progression steps (Solaini et al, 2011;Tasaki et al, 2014;Ziech et al, 2010). Concerning DNA damage related to ROS activity, it may implicate breaks in single or double stranded DNA chain and adjustments in deoxyribose or nitrogenous bases.…”

Section: Introductionmentioning

confidence: 99%

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N-diethylnitrosamine mouse hepatotoxicity: Time-related effects on histology and oxidative stress

Santos

Colaço

Costa

et al. 2014

Experimental and Toxicologic Pathology

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Animal models, namely mice, have been used to study chemically induced carcinogenesis due to their similarity to the histological and genetic features of human patients. Hepatocellular carcinoma (HCC) is a common malignancy with poor clinical outcome. The high incidence of HCC might be related to expo-sure to known risk factors, including carcinogenic compounds, such as N-nitrosamines, which cause DNA damage. N-nitrosamines affect cell mitochondrial metabolism, disturbing the balance between reactive oxygen species (ROS) and antioxidants, causing oxidative stress and DNA damage, potentially leading to carcinogenesis. This work addresses the progressive histological changes in the liver of N-diethylnitrosamine (DEN)-exposed mice and its correlation with oxidative stress.Male ICR mice were randomly divided into five DEN-exposed and five matched control groups. DEN was IP administered, once a week, for eight consecutive weeks.2 Samples were taken 18 h after the last DEN injection (8 weeks post-exposure). The following sampling occurred at weeks 15th, 22nd, 29th and 36th after the first DEN injection. DEN resulted in early toxic lesions and, from week 29 onwards, in progressive proliferative lesions. Between 15 and 29 weeks, DEN-exposed animals showed significant changes in hepatic antioxidant (glutathione, glutathione reductase, and catalase) status (p < 0.05) compared with controls. These results point to an association between increased DEN-induced oxidative stress and the early histopathological alterations, suggesting that DEN disrupted the antioxidant defense mechanism, thereby triggering liver carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

N-diethylnitrosamine mouse hepatotoxicity: Time-related effects on histology and oxidative stress

Santos

Colaço

Costa

et al. 2014

Experimental and Toxicologic Pathology

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“…Individuals carrying the NQO1 variant allele and genotypes are more susceptible to HCC [76] . Oxidative stress promotes the proliferation of preneoplastic lesions and their progression to neoplasms [77] . HCC development is accompanied by a continuous increase in ROS levels [78][79][80][81] .…”

Section: Ros and Hepatocarcinomamentioning

confidence: 99%

ROS correlates intimately with the progression of non-alcoholic fatty liver disease to hepatocarcinoma

Yuan¹,

Li²,

Dong³

2015

Can Cell Microenviron

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The prevalence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing. NAFLD affects the health of one-third of the world's population in forms that range from simple steatosis to hepatocellular injury, inflammation, fibrosis, liver cirrhosis and hepatocarcinoma. Oxidative stress in the progression of NAFLD to hepatocarcinoma is gaining increasing attention. Sustained and excessive reactive oxygen species (ROS), which lead to oxidative stress, are involved in all pathophysiological stages of NAFLD and contribute to the occurrence of hepatocarcinoma. Antioxidants in natural plant extracts that activate nuclear factor related to E2 factor 2 (Nrf2) can effectively suppress the progression. The cellular anti-oxidative system has great importance in the prevention and reversal of NAFLD. This review summarizes the current knowledge of the involvement of oxidative stress in NAFLD to hepatocarcinoma. To cite this article: Yuan Yan, et al. ROS correlates intimately with the progression of non-alcoholic fatty liver disease to hepatocarcinoma.

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“…These enzymes exert cytoprotective, antioxidant and anti-inflammatory effects in the respiratory system ( 6 ). Upregulation and activation of Nrf2 enhances expression of antioxidant genes and protects cells from oxidative injury ( 7 ). Thus, Nrf2 is an important link between the regulation of antioxidant gene expression and cell survival ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Sulforaphane increases Nrf2 expression and protects alveolar epithelial cells against injury caused by cigarette smoke extract

Zhang

Chang

et al. 2017

Molecular Medicine Reports

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Cigarette smoking is a primary risk factor for chronic obstructive pulmonary disease (COPD), as it damages epithelial cells through a variety of mechanisms. Sulforaphane (SFN) is an antioxidant agent, which exerts protective effects against cell damage by activating the nuclear factor erythroid 2 like 2 (NFE2L2; Nrf2). The present study was undertaken to investigate the effects and underlying mechanisms of SFN in preventing cigarette smoke extract (CSE)-induced oxidative damage to RLE-6TN rat lung epithelial cells. MTT assay was used to determine the cytotoxicity of SFN and CSE. The effect of SFN and CSE on cell cycle progression, apoptosis and intracellular reactive oxygen species (ROS) levels were analyzed using flow cytometry. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to quantify mRNA and protein expression levels of Nrf2 respectively. SFN protected RLE-6TN cells from oxidative damage, potentially via increasing Nrf2 expression and reducing ROS levels. In addition, SFN attenuated G1 phase cell cycle arrest and abrogated apoptosis. Therefore, SFN protected alveolar epithelial cells against CSE-induced oxidative injury by upregulating Nrf2 expression. The results of the present study may provide theoretical support for the clinical use of SFN in patients with COPD.

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Lack of nrf2 results in progression of proliferative lesions to neoplasms induced by long-term exposure to non-genotoxic hepatocarcinogens involving oxidative stress

Cited by 19 publications

References 50 publications

N-diethylnitrosamine mouse hepatotoxicity: Time-related effects on histology and oxidative stress

N-diethylnitrosamine mouse hepatotoxicity: Time-related effects on histology and oxidative stress

ROS correlates intimately with the progression of non-alcoholic fatty liver disease to hepatocarcinoma

Sulforaphane increases Nrf2 expression and protects alveolar epithelial cells against injury caused by cigarette smoke extract

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