Dataset Information

Detection of DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a toxicity bioindicator to the effects of nickel on Ni-Cr alloy prosthesis users.

ABSTRACT: Previous studies have suggested that exposure to Ni from Ni-Cr alloys can affect the human body through oxidative stress. The present study discusses the effect of nickel from Ni-Cr alloy prostheses on the formation of DNA Adduct 8-Hydroxy-2'-Deoxyguanosine (8-OHdG), evaluated based on creatinine and 8-OHdG concentrations in urine, determined with LC-MS/MS, for a Ni-Cr alloy user group and a never-user control group. The mean creatinine and 8-OHdG concentrations were not significantly different between the test groups, although highest levels were observed for the in the Ni-Cr user group. It is suggested that samples with relatively high creatinine and/or 8-OHdG levels are further studied in more detail for stability of concentrations and for the effect of contributing factors.

SUBMITTER: Utari DR

PROVIDER: S-EPMC7253878 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Detection of DNA <i>adduct 8-hydroxy-2'-deoxyguanosine</i> (8-OHdG) as a toxicity bioindicator to the effects of nickel on Ni-Cr alloy prosthesis users.

Utari Dian Retno DR Budiawan Auerkari Elza Ibrahim EI

Saudi journal of biological sciences 20200312 6

Previous studies have suggested that exposure to Ni from Ni-Cr alloys can affect the human body through oxidative stress. The present study discusses the effect of nickel from Ni-Cr alloy prostheses on the formation of DNA Adduct 8-Hydroxy-2'-Deoxyguanosine (8-OHdG), evaluated based on creatinine and 8-OHdG concentrations in urine, determined with LC-MS/MS, for a Ni-Cr alloy user group and a never-user control group. The mean creatinine and 8-OHdG concentrations were not significantly different ...[more]

PMID: 32489306

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Project description:PurposeTo investigate systemic oxidative stress-induced DNA damage in patients with pseudoexfoliation glaucoma (PXG), we estimated plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a marker for oxidative DNA damage in comparison to controls. In addition, we also examined a combined effect of lysyl oxidase-like 1 (LOXL1) polymorphism status and 8-OHdG levels on PXG risk.Materials and methodsA retrospective case-control study was performed to estimate plasma levels of 8-OHdG in 41 PXG patients and 45 nonglaucomatous controls using the enzyme-linked immunosorbent assay (ELISA). The assay was performed in duplicate on an automated ELISA analyzer. Two common polymorphisms (rs1048661 and rs3835942) in LOXL1 gene were genotyped by Sanger sequencing.ResultsThe mean and median levels of 8-OHdG were significantly increased in the PXG cases (p=0.032) and male subjects (p=0.041). Subjects with levels greater than the third quartile (75% percentile) exhibited a significant increased risk of PXG (odds ratio = 4.06, 95% confidence interval (CI = 1.11-14.80, p=0.029)). Within- and between-group comparisons showed that the mean levels were higher in individuals carrying the LOXL1 risk variant (G/G), but not statistically significant. In logistic regression analysis, both 8-OHdG (p=0.044) and rs3835942 (p=0.012) showed a statistically significant effect on the PXG outcome. However, the effect was lost when age, sex, and rs1048661 were included. A significant positive correlation was observed between 8-OHdG levels and intraocular pressure (R=0.284, p=0.008) and cup/disc ratio (R=0.233, p=0.031). Furthermore, in receiver operating characteristic analysis, the area under the curve was statistically significant (p=0.032) with a value of 0.635 (95% CI = 0.518-0.751).ConclusionThe study demonstrates an association of increased plasma levels of 8-OHdG in patients with PXG, supporting the role of oxidative stress, and increased oxidative DNA damage in PXG development.

Project description:Oxidative stress is an important toxicity and genotoxicity mechanism of many chronic adverse health outcomes. This study developed a sensitive extraction method for urine matrix (based on lyophilization, without the need for pre-cleaning by solid phase extraction), coupled to LC-MS/MS analysis of the biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG). The methodology was validated in urine samples from a cohort of Spanish pregnant women collected during the first, second and third trimester of pregnancy, and urine samples collected within 24 h after delivery (n = 85). A detection and quantification limit of 0.01 and 0.05 μg/L, respectively, were established. The median 8-OHdG concentration was 2.18 μg/L (range 0.33-7.79); and the corresponding creatinine-adjusted concentrations ranged from 1.04 to 13.12 with median of 4.48 μg 8-OHdG/g creatinine. The concentrations of non-adjusted 8-OHdG significantly decreased (p < 0.05) in the 3rd trimester and post-delivery urine samples when compared to the 1st trimester levels. 8-OHdG concentrations were further studied in placenta samples matching the same urine samples (n = 26), with a median value of 1.3 ng 8-OHdG/g of tissue. Placental 8-OHdG concentrations were correlated with urinary levels of non-adjusted 8-OHdG in the 3rd trimester. Considering the small cohort size, results must be interpreted with caution, however statistical analyses revealed elevated urinary non-adjusted 8-OHdG levels in the 1st trimester of mothers that delivered boys compared to those who delivered girls (p < 0.01). Increased urinary non-adjusted 8-OHdG concentrations at the time of delivery were significantly associated with clinical records (any type of clinical record during pregnancy; p < 0.05). The novel extraction and analytical method for the assessment of 8-OHdG is applicable for sensitive analysis of multiple analytes or biomarkers in urine matrix. This method could also be applied for other matrices such as blood or tissues. Our findings show that 8-OHdG in urine of pregnant women could predict oxidative stress in placenta and can be related to characteristics such as maternal obesity, mode of delivery and newborn sex.

Dataset Information

Detection of DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a toxicity bioindicator to the effects of nickel on Ni-Cr alloy prosthesis users.

Publications

Detection of DNA <i>adduct 8-hydroxy-2'-deoxyguanosine</i> (8-OHdG) as a toxicity bioindicator to the effects of nickel on Ni-Cr alloy prosthesis users.

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