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Iron Overload Is Associated with Hepatic Oxidative Damage to DNA in Nonalcoholic Steatohepatitis
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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“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)
In the citing paper
“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
In the citing paper
“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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Metadata
- Authors
- Fujita, N., Miyachi, H., Tanaka, H., Takeo, M., Nakagawa, N., Kobayashi, Y., Iwasa, M., Watanabe, S., & Takei, Y.
- Affiliations
- Mie University (JP)
- Venue
- Cancer Epidemiology, Biomarkers & Prevention
- Published
- 2009-02-01
- Volume
- 18
- Issue
- 2
- Pages
- 424-432
- ISSN
- 1055-9965 (ISSN-L)
- 1538-7755
- 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 › Hepatology › 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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