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CSF isoprostane levels are a biomarker of oxidative stress in multiple sclerosis.

Mir F, Lee D, Ray H, Sadiq SA - Neurol Neuroimmunol Neuroinflamm (2014)

Bottom Line: We found increased CSF levels of 8-iso-PGF2α in patients with MS compared to controls, with the most striking values in a subgroup of patients with SPMS.Furthermore, the increase in 8-iso-PGF2α correlated with other parameters of lipid peroxidation as well as with a decrease in the total antioxidant status in the MS CSF samples.Further investigation will help establish the pathologic and clinical significance of our preliminary findings.

View Article: PubMed Central - PubMed

Affiliation: Tisch MS Research Center of New York, New York, NY.

ABSTRACT

Objective: To investigate the potential of 8-iso-prostaglandin F2α (8-iso-PGF2α) as a biomarker for disease activity and oxidative stress in the CSF of patients with multiple sclerosis (MS).

Methods: The isoprostane 8-iso-PGF2α is an established biomarker for in vivo oxidative stress and lipid peroxidation. We measured CSF 8-isoPGF2α levels in 231 patients with MS (74 with relapsing-remitting MS, 67 with primary progressive MS, and 90 with secondary progressive MS [SPMS]) and 40 controls using a competition ELISA.

Results: We found increased CSF levels of 8-iso-PGF2α in patients with MS compared to controls, with the most striking values in a subgroup of patients with SPMS. Furthermore, the increase in 8-iso-PGF2α correlated with other parameters of lipid peroxidation as well as with a decrease in the total antioxidant status in the MS CSF samples.

Conclusions: Our study demonstrates that CSF levels of 8-iso-PGF2α may serve as a biomarker of oxidative stress in MS. Further investigation will help establish the pathologic and clinical significance of our preliminary findings.

No MeSH data available.


Related in: MedlinePlus

8-Iso-PGF2α increases in vivo during EAE and during oxidative insult in cell culture(A) 8-Iso-prostaglandin F2α (8-iso-PGF2α) levels in whole-brain lysate of mice induced with experimental allergic encephalomyelitis (EAE) was induced in 8-week-old mice. Mice were sacrificed at peak of disease (day 15) and whole-brain lysates were prepared. Shown here are the 8-iso-PGF2α levels as determined by ELISA. *** indicates statistical significance with a p value of <0.05. (B) 8-Iso-PGF2α is produced by glial cells under oxidative stress conditions. The glial cell line CG4 was subjected to oxidative stress in culture by the addition of 50 µM hydrogen peroxide (H2O2) or the reactive oxygen generator 2,2′-azobis-2-methyl-propanimidamide dihydrochloride AAPH). Reactive oxygen species (ROS) scavenger EUK134 was added to quench the ROS released. The 8-iso-PGF2α levels were then assayed in the cell culture medium by ELISA. The experiment is a mean of n = 3 and *** indicates statistical significance with a p value of <0.05.
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Figure 4: 8-Iso-PGF2α increases in vivo during EAE and during oxidative insult in cell culture(A) 8-Iso-prostaglandin F2α (8-iso-PGF2α) levels in whole-brain lysate of mice induced with experimental allergic encephalomyelitis (EAE) was induced in 8-week-old mice. Mice were sacrificed at peak of disease (day 15) and whole-brain lysates were prepared. Shown here are the 8-iso-PGF2α levels as determined by ELISA. *** indicates statistical significance with a p value of <0.05. (B) 8-Iso-PGF2α is produced by glial cells under oxidative stress conditions. The glial cell line CG4 was subjected to oxidative stress in culture by the addition of 50 µM hydrogen peroxide (H2O2) or the reactive oxygen generator 2,2′-azobis-2-methyl-propanimidamide dihydrochloride AAPH). Reactive oxygen species (ROS) scavenger EUK134 was added to quench the ROS released. The 8-iso-PGF2α levels were then assayed in the cell culture medium by ELISA. The experiment is a mean of n = 3 and *** indicates statistical significance with a p value of <0.05.

Mentions: To determine whether 8-iso-PGF2α levels are increased in experimental models of demyelination, we measured levels of 8-iso-PGF2α in whole-brain lysate of mice induced with EAE and compared the values to those in the brain lysates of control mice (figure 4A). The EAE mice were sacrificed at disease peak (i.e., on day 15) and had a mean disability score of 7.8 ± 2.1 on a 0–13 scale.22,23 In EAE, levels of 8-iso-PGF2α (0.784 ± 0.03 pg/mg tissue) at peak of disease (day 15) were higher (p < 0.003 value) than the levels in control mice (0.372 ± 0.71 pg/mg tissue).


CSF isoprostane levels are a biomarker of oxidative stress in multiple sclerosis.

Mir F, Lee D, Ray H, Sadiq SA - Neurol Neuroimmunol Neuroinflamm (2014)

8-Iso-PGF2α increases in vivo during EAE and during oxidative insult in cell culture(A) 8-Iso-prostaglandin F2α (8-iso-PGF2α) levels in whole-brain lysate of mice induced with experimental allergic encephalomyelitis (EAE) was induced in 8-week-old mice. Mice were sacrificed at peak of disease (day 15) and whole-brain lysates were prepared. Shown here are the 8-iso-PGF2α levels as determined by ELISA. *** indicates statistical significance with a p value of <0.05. (B) 8-Iso-PGF2α is produced by glial cells under oxidative stress conditions. The glial cell line CG4 was subjected to oxidative stress in culture by the addition of 50 µM hydrogen peroxide (H2O2) or the reactive oxygen generator 2,2′-azobis-2-methyl-propanimidamide dihydrochloride AAPH). Reactive oxygen species (ROS) scavenger EUK134 was added to quench the ROS released. The 8-iso-PGF2α levels were then assayed in the cell culture medium by ELISA. The experiment is a mean of n = 3 and *** indicates statistical significance with a p value of <0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 4: 8-Iso-PGF2α increases in vivo during EAE and during oxidative insult in cell culture(A) 8-Iso-prostaglandin F2α (8-iso-PGF2α) levels in whole-brain lysate of mice induced with experimental allergic encephalomyelitis (EAE) was induced in 8-week-old mice. Mice were sacrificed at peak of disease (day 15) and whole-brain lysates were prepared. Shown here are the 8-iso-PGF2α levels as determined by ELISA. *** indicates statistical significance with a p value of <0.05. (B) 8-Iso-PGF2α is produced by glial cells under oxidative stress conditions. The glial cell line CG4 was subjected to oxidative stress in culture by the addition of 50 µM hydrogen peroxide (H2O2) or the reactive oxygen generator 2,2′-azobis-2-methyl-propanimidamide dihydrochloride AAPH). Reactive oxygen species (ROS) scavenger EUK134 was added to quench the ROS released. The 8-iso-PGF2α levels were then assayed in the cell culture medium by ELISA. The experiment is a mean of n = 3 and *** indicates statistical significance with a p value of <0.05.
Mentions: To determine whether 8-iso-PGF2α levels are increased in experimental models of demyelination, we measured levels of 8-iso-PGF2α in whole-brain lysate of mice induced with EAE and compared the values to those in the brain lysates of control mice (figure 4A). The EAE mice were sacrificed at disease peak (i.e., on day 15) and had a mean disability score of 7.8 ± 2.1 on a 0–13 scale.22,23 In EAE, levels of 8-iso-PGF2α (0.784 ± 0.03 pg/mg tissue) at peak of disease (day 15) were higher (p < 0.003 value) than the levels in control mice (0.372 ± 0.71 pg/mg tissue).

Bottom Line: We found increased CSF levels of 8-iso-PGF2α in patients with MS compared to controls, with the most striking values in a subgroup of patients with SPMS.Furthermore, the increase in 8-iso-PGF2α correlated with other parameters of lipid peroxidation as well as with a decrease in the total antioxidant status in the MS CSF samples.Further investigation will help establish the pathologic and clinical significance of our preliminary findings.

View Article: PubMed Central - PubMed

Affiliation: Tisch MS Research Center of New York, New York, NY.

ABSTRACT

Objective: To investigate the potential of 8-iso-prostaglandin F2α (8-iso-PGF2α) as a biomarker for disease activity and oxidative stress in the CSF of patients with multiple sclerosis (MS).

Methods: The isoprostane 8-iso-PGF2α is an established biomarker for in vivo oxidative stress and lipid peroxidation. We measured CSF 8-isoPGF2α levels in 231 patients with MS (74 with relapsing-remitting MS, 67 with primary progressive MS, and 90 with secondary progressive MS [SPMS]) and 40 controls using a competition ELISA.

Results: We found increased CSF levels of 8-iso-PGF2α in patients with MS compared to controls, with the most striking values in a subgroup of patients with SPMS. Furthermore, the increase in 8-iso-PGF2α correlated with other parameters of lipid peroxidation as well as with a decrease in the total antioxidant status in the MS CSF samples.

Conclusions: Our study demonstrates that CSF levels of 8-iso-PGF2α may serve as a biomarker of oxidative stress in MS. Further investigation will help establish the pathologic and clinical significance of our preliminary findings.

No MeSH data available.


Related in: MedlinePlus