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Cited by 107Liver Disease Diagnosis and TreatmentIron Metabolism and DisordersLiver physiology and pathology

Iron Overload Is Associated with Hepatic Oxidative Damage to DNA in Nonalcoholic Steatohepatitis

Fujita, Naoki, Miyachi, Hirohide, Tanaka, Hideaki, Takeo, Masaki, Nakagawa, Naoki, Kobayashi, Yoshinao, Iwasa, Motoh, Watanabe, Shozo +1 more·2009·Cancer Epidemiology, Biomarkers & Prevention
DOI 10.1158/1055-9965.epi-08-0725
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Abstract

Several lines of evidence have suggested that oxidative stress plays an important role for the pathogenesis of nonalcoholic steatohepatitis (NASH). Therefore, by using immunohistochemical staining of liver biopsy samples, we measured hepatic 7,8-dihydro-8-oxo-2′ deoxyguanosine (8-oxodG), a DNA base-modified product generated by hydroxyl radicals, of 38 NASH patients and compared with 24 simple steatosis and 10 healthy subjects. Relation of hepatic 8-oxodG with clinical, biochemical, and histologic variables and changes after iron reduction therapy (phlebotomy plus iron–restricted diet) were also examined. Hepatic 8-oxodG levels were significantly higher in NASH compared with simple steatosis (17.5 versus 2.0 8-oxodG–positive cells/105 μm2; P < 0.0001). 8-oxodG was significantly related to iron overload condition, glucose-insulin metabolic abnormality, and severities of hepatic steatosis in NASH patients. Logistic regression analysis also showed that hepatic iron deposit and insulin resistance were independent variables associated with elevated hepatic 8-oxodG. After the iron reduction therapy, hepatic 8-oxodG levels were significantly decreased (from 20.7 to 13.8 positive cells/105 μm2; P < 0.01) with concomitant reductions of serum transaminase levels in NASH patients. In conclusion, iron overload may play an important role in the pathogenesis of NASH by generating oxidative DNA damage and iron reduction therapy may reduce hepatocellular carcinoma incidence in patients with NASH. (Cancer Epidemiol Biomarkers Prev 2009;18(2):424–32)

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Crossref · 10.1158/1055-9965.epi-08-0725

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  • In steatosis, saturation of the beta-oxidation pathway with excess free fatty acids leads to further generation of H2O2 and other ROS.

    “These authors also reported that in steatosis, saturation of the -oxidation pathway with excess free fatty acids leads to further generation of H 2 O 2 , and other ROS.”

    From Iron, Oxidative Stress and Health (2012) · cites this paper as Fujita et al.,(2009)

  • Circulating prohepcidin is associated with parameters of glucose and iron metabolism in subjects with altered glucose tolerance.

    “Circulating prohepcidin was reported to be associated with parameters of glucose and iron metabolism, in subjects with altered glucose tolerance (Fujita et al., 2009).”

    From Iron, Oxidative Stress and Health (2012) · cites this paper as Fujita et al., 2009

  • NASH patients have elevated levels of hepatic 8-oxodG, a DNA base-modified product generated by hydroxyl radicals, and the level of this product is reduced by iron reduction therapy.

    “Further, Fujita et al.,(2009) reported that NASH patients had elevated levels of hepatic 8-oxodG which is is a DNA base-modified product generated by hydroxyl radicals.The level of this product was reduced by iron reduction therapy.”

    From Iron, Oxidative Stress and Health (2012) · cites this paper as Fujita et al.,(2009)

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Authors
Fujita, N., Miyachi, H., Tanaka, H., Takeo, M., Nakagawa, N., Kobayashi, Y., Iwasa, M., Watanabe, S., & Takei, Y.
Affiliations
Mie University (JP)
ORCID
Venue
Cancer Epidemiology, Biomarkers & Prevention
Publisher
American Association for Cancer Research (AACR)
Published
2009-02-01
Volume
18
Issue
2
Pages
424-432
ISSN
  • 1055-9965 (ISSN-L)
  • 1538-7755
DOI
10.1158/1055-9965.epi-08-0725
OpenAlex
W2164144565
Cited by
107
References
40
Citations by year
2026: 4 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 8 · 2018: 8 · 2017: 5 · 2016: 10 · 2015: 9 · 2014: 7 · 2013: 7 · 2012: 6
FWCI
6.30
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer Epidemiology Biomarkers & Prevention (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
nonalcoholic steatohepatitis, iron overload, oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, oxidative stress, phlebotomy, insulin resistance, hepatic steatosis, hepatocellular carcinoma risk, hydroxyl radicals
MeSH terms
8-Hydroxy-2'-Deoxyguanosine, Adult, Aged, Analysis of Variance, Deoxyguanosine, DNA Damage, Fatty Liver, Female, Carcinoma, Hepatocellular, Humans, Insulin Resistance, Liver Function Tests, Liver Neoplasms, Male, Middle Aged, Severity of Illness Index, Logistic Models, Case-Control Studies, Oxidative Stress, Statistics, Nonparametric, Iron Overload

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