Anti-inflammatory effects of 8-hydroxy-2′-deoxyguanosine on lipopolysaccharide-induced inflammation via Rac suppression in Balb/c mice

Choi, Syngjoo; Choi, Hyun Ho; Lee, Sun Hye; Ko, Seong Hee; You, Ho Jin; Ye, Sang Kyu; Chung, Myung Hee

doi:10.1016/j.freeradbiomed.2007.08.022

Cited by 48 publications

(35 citation statements)

References 44 publications

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“…Importantly in our study, the sensitivity of 8-OHdG is such that we observed a significant elevation in the prediabetic group compared with the controls despite good HbA1c readings in all groups. An elevation of 8-OHdG indicates an increase in the degree of oxidative stress affecting tissue function and integrity and therefore provides useful information on oxidative stress and disease progression (31). Our current findings agree with the earlier work (32); however, the prediabetic group in this study was defined according to the WHO criteria with blood glucose ranging between 6 and 7 mmol/l (20), whereas we used the ADA classification of prediabetes in the previous study with blood glucose ranging between 5.5 and 7 mmol/l.…”

Section: Discussionmentioning

confidence: 99%

Oxidative DNA damage and obesity in type 2 diabetes mellitus

Al-Aubaidy

Jelinek²

2011

European Journal of Endocrinology

154

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Objective: This study illustrates the relationship between oxidative DNA damage and obesity in patients with prediabetes and type 2 diabetes compared with controls. Design and methods: Participants attended the School of Community Health, Diabetes Screening Clinic, Charles Sturt University, Australia, between February 2006 and June 2008. A total of 162 participants (35 type 2 diabetic patients; eight prediabetic subjects; and 119 age-, gender-, and weight-matched controls) were investigated. All patients were selected on clinical grounds. Results: Serum 8-hydroxy 2 0 -deoxy-guanosine (8-OHdG) level was significantly greater in the prediabetic subjects (671.3G140 pg/ml) compared with controls (210.1G166 pg/ml; P!0.01). The diabetic group (1979.6G1209 pg/ml) had the highest level of 8-OHdG. There was a significant increase in serum 8-OHdG in obese subjects (848.5G103 pg/ml; P!0.001) and overweight subjects (724G102 pg/ml; PZ0.005) compared with the lean subjects (196.5G327 pg/ml). Conclusion: Our results indicate that serum 8-OHdG is increased already in prediabetes suggesting oxidative DNA damage to be present with minor elevation of blood glucose levels (BGLs). The statistically significant positive correlation between serum 8-OHdG and body mass index in the diabetic group indicates that obesity has an additive effect to increased BGL contributing to oxidative DNA damage. European Journal of Endocrinology 164 899-904

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Section: Discussionmentioning

confidence: 99%

Oxidative DNA damage and obesity in type 2 diabetes mellitus

Al-Aubaidy

Jelinek²

2011

European Journal of Endocrinology

154

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“…In summary, the significance of our study is that we were successful in not only documenting the cancer-preventive effect of CAC with exogenous 8-OHdG, formerly recognized as the product of oxidative stress, but also elucidating the core pharmacologic actions of 8-OHdG, paradoxically antioxidative and anti-inflammatory (19)(20)(21)(22) actions such as the regulation of Rac1-STAT3, NOX4, b-catenin, MMP, and COX-2, key mediators reported to be principally engaged in colon carcinogenesis.…”

Section: Discussionmentioning

confidence: 89%

“…Although the clinical significance of 8-OHdG as biomarker for oxidative stress has been well studied and associated with inflammation, mutagenesis, and carcinogenesis because it is easily detected in sera or urine of patients by its membrane permeability (33-35) because 8-OHdG might incorporate into genomic DNA, causing transversion mutation (36,37), our group has clearly reported that paradoxically exogenous 8-OHdG exerted anti-inflammatory and antioxidant action in various kinds of inflammation-based animal model as well as in vitro experiment (19)(20)(21)(22). Because exogenous 8-OHdG is not salvaged into genomic DNA, as it is to be neither degraded into 8-oxo-7,8-dihydroguanine nor phosphorylated into 8-oxo-7,8-dihydroguanine triphosphate and it indeed never does seem to incorporate into nucleus compared with deoxyguanosine control (38, 39), 8-OHdG can be a novel drug candidate.…”

Section: Discussionmentioning

confidence: 99%

“…Although 8-hydroxydeoxyguanosine (8-oxo-7,8-dihydrodeoxyguanosine or 8-OHdG) has been acknowledged as a sensitive marker for oxidative stress, a potent mutagen or a toxic product, we previously published that 8-OHdG specifically inhibits Rac1/2, the members of small GTPase family that play a crucial role of generating reactive oxygen species (ROS) by activating NADPH oxidase (NOX) complex, subsequently regulating redox-sensitive NF-kB pathway, in not only in vitro macrophage cell lines but also animal model of lipopolysaccharide (LPS)-induced septicemia and ovalbumin-sensitized allergic reaction as well as water immersion-restraint stressinduced gastritis (19)(20)(21)(22). In addition, Simon and colleagues (23) showed that Rac1 directly binds and activates STAT3 and the inhibition of Rac1 by exogenous treatment with 8-OHdG affects STAT3 signal pathway, which may regulate the genes associated with inflammation-dysplasia-carcinoma sequence.…”

Section: Introductionmentioning

confidence: 99%

“…All of these backgrounds led us to investigate the hypothesis that exogenous administration of 8-OHdG might have the preventive effect on the animal model of colitic cancer based on its potent anti-inflammatory and antioxidative actions (19)(20)(21)(22). Using dextran sodium sulfate (DSS)-induced colitis and 2-stage colon cancer model first established by Tanaka and colleagues (24), in which colon cancer is initiated by azoxymethane (AOM) and promoted by DSS ingestion, we studied whether exogenous 8-OHdG is effective in ameliorating colitis, after which long-term administration of 8-OHdG-containing diet can prevent colitis-associated cancer in interleukin (IL)-10 knockout mice to prove the potential role of exogenous 8-OHdG as a natural terminator or means of negative feedback of inflammation in chronic inflammation-carcinogenesis sequence.…”

Section: Introductionmentioning

confidence: 99%

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Prevention of Colitis-Associated Colorectal Cancer with 8-Hydroxydeoxyguanosine

Ock

Kim²,

Hong³

et al. 2011

Cancer Prevention Research

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Colitis-associated cancer (CAC) is one of clear examples of inflammation-carcinogenesis sequence, by which the strict control of colitis with potent anti-inflammatory or antioxidative agent offers the chance of cancer prevention. Supported with the facts that Rac1 binds and activates STAT3, which are significantly upregulated in inflammatory bowel disease (IBD) as well as CAC, but 8-hydroxydeoxyguanosine (8-oxo-7,8-dihydrodeoxyguanosine or 8-OHdG) paradoxically can block Rac1 activation and subsequent NADPH oxidase (NOX) inactivation in various inflammation models, we hypothesized that attenuated Rac1-STAT3 and COX-NF-kB pathway by exogenous 8-OHdG administration may ameliorate inflammatory signaling in dextran sodium sulfate (DSS)-induced colitis and can prevent CAC. Before commencing carcinogenesis model, we checked whether exogenous 8-OHdG can alleviate IBD, for which interleukin (IL)-10 knockout mice were designed to ingest 5% DSS for 1 week, and 8-OHdG is given through intraperitoneal route daily. 8-OHdG treatment groups significantly reduced pathologic grade of DSSinduced colitis as well as various inflammatory mediators such as TNF-a, IL-6, COX-2, and iNOS in a dose-dependent manner. To document the cancer prevention effects of 8-OHdG, mice were injected azoxymethane followed by drinking 2.5% DSS for 1 week, after which 8-OHdG-containing diets were given for 20 weeks. As results, mice that consumed 8-OHdG-containing diet significantly reduced both tumor incidence and multiplicity. Rac1 activity and phosphorylated STAT3 level were significantly attenuated in the 8-OHdG-treated group. Significantly decreased levels of malondialdehyde, monocyte chemotactic protein-1, matrix metalloproteinasess, COX-2, NOX4, and b-catenin nuclear accumulation were responsible for cancer prevention effects of exogenous 8-OHdG. In conclusion, we clearly showed cancer-preventive effect of exogenous 8-OHdG against CAC. Cancer Prev Res; 4(9); 1507-21. Ó2011 AACR.

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Lipid peroxidation mediates the association between iron overload and liver injury: cross-sectional and longitudinal analyses in general Chinese urban adults

Wang

Cheng

et al. 2023

Environ Sci Pollut Res

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Background: Iron overload has been associated with acute/chronic organ failure, but whether iron overload induces liver injury remain unclear.Objectives: To assess the relationship between urinary iron and serum alanine aminotransferase (ALT, a biomarker for liver injury), and investigate the potential mediating roles of lipid peroxidation and oxidative DNA damage in such association.Methods: Levels of urinary iron, serum ALT, and urinary biomarkers of lipid peroxidation (8-isoprostaglandin-F 2α [8-iso-PGF 2α ]) and oxidative DNA damage (8-hydroxy-deoxyguano-sine [8-OHdG]) were measured among 5386 observations of 4220 participants from the Wuhan-Zhuhai cohort. The relationships between urinary iron and serum ALT as well as risk of hyperALT were separately evaluated by linear mixed models and logistic regression models. The mediating roles of 8-iso-PGF 2α and 8-OHdG were assessed by mediation analyses.Results: In cross sectional analysis, urinary iron was positively associated with ALT (β=0.032; 95% CI: 0.020, 0.044) and hyperALT (OR=1.127; 95% CI: 1.065, 1.192). After 3 years of follow-up, participants with persistent high iron level had increased risk of developing hyperALT (RR=3.800; 95% CI: 1.464, 9.972) when compared with those with persistent low iron level. In addition, each 1% increase in urinary iron was associated with a 0.146% (95% CI: 0.128%, 0.164%) and 0.192% (95% CI: 0.154%, 0.229%) increase in 8iso-PGF 2α and 8-OHdG, respectively. Urinary 8-iso-PGF 2α (β=0.056; 95% CI: 0.039, 0.074) rather than 8-OHdG was positively associated with ALT, and increased 8-iso-PGF 2α signi cantly mediate 22.48% of the urinary iron-associated ALT increment.Conclusions: Our study demonstrated that iron overload was signi cantly associated with liver injury, which was partly mediated by lipid peroxidation.

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Anti-inflammatory effects of 8-hydroxy-2′-deoxyguanosine on lipopolysaccharide-induced inflammation via Rac suppression in Balb/c mice

Cited by 48 publications

References 44 publications

Oxidative DNA damage and obesity in type 2 diabetes mellitus

Oxidative DNA damage and obesity in type 2 diabetes mellitus

Prevention of Colitis-Associated Colorectal Cancer with 8-Hydroxydeoxyguanosine

Lipid peroxidation mediates the association between iron overload and liver injury: cross-sectional and longitudinal analyses in general Chinese urban adults

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