ABSTRACT
AIM: To provide an up-to-date review of oxidative stress biomarkers in multiple sclerosis and thus identify candidate molecules with greatest promise as biomarkers of diagnosis, disease activity or prognosis. METHOD: A semi-systematic literature search using PubMed and other databases. RESULTS: Nitric oxide metabolites, superoxide dismutase, catalase, glutathione reductase, inducible nitric oxide synthase, protein carbonyl, 3-nitrotyrosine, isoprostanes, malondialdehyde and products of DNA oxidation have been identified across multiple studies as having promise as diagnostic, therapeutic or prognostic markers in MS. CONCLUSION: Heterogeneity of study design, particularly patient selection, limits comparability across studies. Further cohort studies are needed, and we would recommend promising markers be incorporated into future clinical trials to prospectively validate their potential.
Subject(s)
Biomarkers/analysis , Multiple Sclerosis/diagnosis , Oxidative Stress , Biomarkers/blood , Biomarkers/cerebrospinal fluid , DNA/chemistry , Humans , Malondialdehyde/blood , Malondialdehyde/cerebrospinal fluid , Multiple Sclerosis/pathology , Nitric Oxide/blood , Nitric Oxide/cerebrospinal fluid , Nitric Oxide Synthase Type II/blood , Nitric Oxide Synthase Type II/cerebrospinal fluid , Protein Carbonylation , Superoxide Dismutase/blood , Superoxide Dismutase/cerebrospinal fluidABSTRACT
Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress, neuronal injury, and inflammation and decreased neurotransmitter levels have been reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have a neuroprotective effect by inhibiting inducible nitric oxide synthase, which produces nitric oxide, a compound that induces oxygen free radical production. In A5235, "Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment," minocycline was not associated with cognitive improvement, but the effect on the above CSF measures was not examined previously. The objective of this study was to examine the effect of minocycline on markers of oxidative stress, neuronal injury, neurotransmitter levels, and inflammation from CSF in participants in A5235. One hundred seven HIV+ individuals received either minocycline 100 mg or placebo orally every 12 h for 24 weeks. Twenty-one HIV+ individuals received the optional lumbar punctures. Lipid and protein markers of oxidative stress (e.g., ceramides and protein carbonyls), glutamate, neurotransmitter precursors, kynurenine metabolites, neurofilament heavy chain, and inflammatory cytokines were measured in the CSF before and after treatment. The 24-week change in ceramides was larger in a beneficial direction in the minocycline group compared to the placebo group. The two groups did not differ in the 24-week changes for other markers.These results suggest that minocycline may decrease lipid markers of oxidative stress (ceramides) in individuals with HAND; however, an effect of minocycline on other CSF markers was not observed. A larger sample size is needed to further validate these results.
Subject(s)
AIDS Dementia Complex/drug therapy , Acquired Immunodeficiency Syndrome/drug therapy , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Minocycline/therapeutic use , Neuroprotective Agents/therapeutic use , AIDS Dementia Complex/cerebrospinal fluid , AIDS Dementia Complex/pathology , AIDS Dementia Complex/virology , Acquired Immunodeficiency Syndrome/cerebrospinal fluid , Acquired Immunodeficiency Syndrome/pathology , Acquired Immunodeficiency Syndrome/virology , Administration, Oral , Adult , Ceramides/cerebrospinal fluid , Cytokines/cerebrospinal fluid , Double-Blind Method , Female , Glutamic Acid/cerebrospinal fluid , HIV-1/drug effects , HIV-1/physiology , Humans , Kynurenine/cerebrospinal fluid , Male , Middle Aged , Neurofilament Proteins/cerebrospinal fluid , Neurons/drug effects , Neurons/pathology , Neurons/virology , Nitric Oxide Synthase Type II/cerebrospinal fluid , Oxidative StressABSTRACT
This study is to investigate the influence and mechanism of action of asymmetrical dimethylarginine (ADMA) and the induced oxidative stress level on Alzheimer's disease (AD) incidence. ADMA concentration, nitric oxide, Abeta(40)/Abeta(42) ratio, inducible NO synthase (iNOS) activity and the concentrations of the induced free radicals including malondialdehyde (MDA), 3-nitrotyrosine (3-NT) and peroxynitrite (ONOO-) in the cerebrospinal fluid (CSF) from 34 neurologically normal controls and 37 AD patients were quantitatively determined and statistically compared. The results showed that the ADMA concentration significantly decreased in AD patients, and it showed negative correlation with the NO, iNOS activity, and showed positive correlation with MMSE score. ADMA concentration was negatively correlated with Abeta(40)/Abeta(42) ratio (P<0.01) with the observation that Abeta(40)/Abeta(42) ratio increased while ADMA level decreased in CSF in AD patients. The concentration levels of MDA, 3-NT and ROS significantly increased compared with the control with all the P values less than 0.05. These findings suggested that the ADMA disorder and the oxidative damage effect of the induced free radicals in CSF of AD patients are an important mechanism of AD incidence, and their joint regulation may provide new idea for the prevention and clinical treatment of AD.
