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Classifying oxidative stress by F 2 -isoprostane levels across human diseases: A meta-analysis

View Article: PubMed Central - PubMed

ABSTRACT

The notion that oxidative stress plays a role in virtually every human disease and environmental exposure has become ingrained in everyday knowledge. However, mounting evidence regarding the lack of specificity of biomarkers traditionally used as indicators of oxidative stress in human disease and exposures now necessitates re-evaluation. To prioritize these re-evaluations, published literature was comprehensively analyzed in a meta-analysis to quantitatively classify the levels of systemic oxidative damage across human disease and in response to environmental exposures.

In this meta-analysis, the F2-isoprostane, 8-iso-PGF2α, was specifically chosen as the representative marker of oxidative damage. To combine published values across measurement methods and specimens, the standardized mean differences (Hedges’ g) in 8-iso-PGF2α levels between affected and control populations were calculated.

The meta-analysis resulted in a classification of oxidative damage levels as measured by 8-iso-PGF2α across 50 human health outcomes and exposures from 242 distinct publications. Relatively small increases in 8-iso-PGF2α levels (g<0.8) were found in the following conditions: hypertension (g=0.4), metabolic syndrome (g=0.5), asthma (g=0.4), and tobacco smoking (g=0.7). In contrast, large increases in 8-iso-PGF2α levels were observed in pathologies of the kidney, e.g., chronic renal insufficiency (g=1.9), obstructive sleep apnoea (g=1.1), and pre-eclampsia (g=1.1), as well as respiratory tract disorders, e.g., cystic fibrosis (g=2.3).

In conclusion, we have established a quantitative classification for the level of 8-iso-PGF2α generation in different human pathologies and exposures based on a comprehensive meta-analysis of published data. This analysis provides knowledge on the true involvement of oxidative damage across human health outcomes as well as utilizes past research to prioritize those conditions requiring further scrutiny on the mechanisms of biomarker generation.

No MeSH data available.


Comparison between standardized mean differences for free and total 8-iso-PGF2α. Data are fixed-effect model Hedges’ g values ±95% confidence interval.
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f0035: Comparison between standardized mean differences for free and total 8-iso-PGF2α. Data are fixed-effect model Hedges’ g values ±95% confidence interval.

Mentions: Total 8-iso-PGF2α represents an aggregate of both free 8-iso-PGF2α and 8-iso-PGF2α esterified to phospholipids. Esterified 8-iso-PGF2α is typically measured as free after liberation by base hydrolysis or upon treatment with a phospholipase. Total 8-iso-PGF2α in plasma is ~10 times the concentration relative to the free 8-iso-PGF2α (Fig. 5). Far fewer publications were found for total 8-iso-PGF2α. These involved 9 conditions. The meta-analysis results for total 8-iso-PGF2α are presented graphically in a Forest plot (Fig. 6). Due to the small number of conditions, it is hard to create a ranking order for categories like the one created for free 8-iso-PGF2α. However, a comparison can be made between the free and total 8-iso-PGF2α for each condition (Fig. 7). Interestingly, in some conditions total 8-iso-PGF2α showed a greater response than free 8-iso-PGF2α. These conditions included tobacco smoking (g=1.3 vs. 0.7) and coronary artery disease (g=1.1 vs. 0.3). In other conditions such as pre-eclampsia (g=1.1 vs. 0.4) and chronic kidney insufficiency (g=1.9 vs. 1.2), the free 8-iso-PGF2α showed a greater response than the total 8-iso-PGF2α.


Classifying oxidative stress by F 2 -isoprostane levels across human diseases: A meta-analysis
Comparison between standardized mean differences for free and total 8-iso-PGF2α. Data are fixed-effect model Hedges’ g values ±95% confidence interval.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384299&req=5

f0035: Comparison between standardized mean differences for free and total 8-iso-PGF2α. Data are fixed-effect model Hedges’ g values ±95% confidence interval.
Mentions: Total 8-iso-PGF2α represents an aggregate of both free 8-iso-PGF2α and 8-iso-PGF2α esterified to phospholipids. Esterified 8-iso-PGF2α is typically measured as free after liberation by base hydrolysis or upon treatment with a phospholipase. Total 8-iso-PGF2α in plasma is ~10 times the concentration relative to the free 8-iso-PGF2α (Fig. 5). Far fewer publications were found for total 8-iso-PGF2α. These involved 9 conditions. The meta-analysis results for total 8-iso-PGF2α are presented graphically in a Forest plot (Fig. 6). Due to the small number of conditions, it is hard to create a ranking order for categories like the one created for free 8-iso-PGF2α. However, a comparison can be made between the free and total 8-iso-PGF2α for each condition (Fig. 7). Interestingly, in some conditions total 8-iso-PGF2α showed a greater response than free 8-iso-PGF2α. These conditions included tobacco smoking (g=1.3 vs. 0.7) and coronary artery disease (g=1.1 vs. 0.3). In other conditions such as pre-eclampsia (g=1.1 vs. 0.4) and chronic kidney insufficiency (g=1.9 vs. 1.2), the free 8-iso-PGF2α showed a greater response than the total 8-iso-PGF2α.

View Article: PubMed Central - PubMed

ABSTRACT

The notion that oxidative stress plays a role in virtually every human disease and environmental exposure has become ingrained in everyday knowledge. However, mounting evidence regarding the lack of specificity of biomarkers traditionally used as indicators of oxidative stress in human disease and exposures now necessitates re-evaluation. To prioritize these re-evaluations, published literature was comprehensively analyzed in a meta-analysis to quantitatively classify the levels of systemic oxidative damage across human disease and in response to environmental exposures.

In this meta-analysis, the F2-isoprostane, 8-iso-PGF2α, was specifically chosen as the representative marker of oxidative damage. To combine published values across measurement methods and specimens, the standardized mean differences (Hedges’ g) in 8-iso-PGF2α levels between affected and control populations were calculated.

The meta-analysis resulted in a classification of oxidative damage levels as measured by 8-iso-PGF2α across 50 human health outcomes and exposures from 242 distinct publications. Relatively small increases in 8-iso-PGF2α levels (g<0.8) were found in the following conditions: hypertension (g=0.4), metabolic syndrome (g=0.5), asthma (g=0.4), and tobacco smoking (g=0.7). In contrast, large increases in 8-iso-PGF2α levels were observed in pathologies of the kidney, e.g., chronic renal insufficiency (g=1.9), obstructive sleep apnoea (g=1.1), and pre-eclampsia (g=1.1), as well as respiratory tract disorders, e.g., cystic fibrosis (g=2.3).

In conclusion, we have established a quantitative classification for the level of 8-iso-PGF2α generation in different human pathologies and exposures based on a comprehensive meta-analysis of published data. This analysis provides knowledge on the true involvement of oxidative damage across human health outcomes as well as utilizes past research to prioritize those conditions requiring further scrutiny on the mechanisms of biomarker generation.

No MeSH data available.