Oxidative Shielding or Oxidative Stress?

Naviaux, Robert K.

doi:10.1124/jpet.112.192120

Cited by 124 publications

(109 citation statements)

References 74 publications

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“…If not already oxidized ex vivo in the supplementation capsules (i.e., becoming rancid), DHA could easily become oxidized after ingestion in vivo, especially given the pro-oxidant state observed in psychiatric disorders (Assies et al 2014). Although supplementation capsules most often contain tocopherols as antioxidants, these probably do not provide full protection against oxidation (Halliwell 2000;Naviaux 2012;Assies et al 2014). Resulting oxidative metabolites of DHA are not yet routinely measured and therefore not completely understood, but may induce negative effects as well (Higdon et al 2012).…”

Section: Role Of Oxidative Stressmentioning

confidence: 99%

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

Mocking

Assies

Ruhé

et al. 2018

J of Inher Metab Disea

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Continuous research into the pathophysiology of psychiatric disorders, such as major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and schizophrenia, suggests an important role for metabolism. This narrative review will provide an upto-date summary of how metabolism is thought to be involved in the pathophysiology of these psychiatric disorders. We will focus on (I) the important role of fatty acids in these metabolic alterations, (II) whether fatty acid alterations represent epiphenomena or risk factors, and (III) similarities and dissociations in fatty acid alterations between different psychiatric disorders. (Historical) epidemiological evidence links fatty acid intake to psychiatric disorder prevalence, corroborated by altered fatty acid concentrations measured in psychiatric patients. These fatty acid alterations are connected with other concomitant pathophysiological mechanisms, including biological stress (hypothalamic-pituitary-adrenal (HPA)-axis and oxidative stress), inflammation, and brain network structure and function. Metabolomics and lipidomics studies are underway to more deeply investigate this complex network of associated neurometabolic alterations. Supplementation of fatty acids as disease-modifying nutraceuticals has clinical potential, particularly add-on eicosapentaenoic acid (EPA) in depressed patients with markers of increased inflammation. However, by interpreting the observed fatty acid alterations as partly (mal)adaptive phenomena, we attempt to nuance translational expectations and provide new clinical applications for these novel neurometabolic insights, e.g., to predict treatment response or depression recurrence. In conclusion, placing fatty acids in context can contribute to further understanding and optimized treatment of psychiatric disorders, in order to diminish their overwhelming burden of disease.

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Section: Role Of Oxidative Stressmentioning

confidence: 99%

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

Mocking

Assies

Ruhé

et al. 2018

J of Inher Metab Disea

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“…These metabolic pathways traced to mitochondria. Mitochondria are responsible for initiating and coordinating innate immunity18 and produce stereotyped changes in oxidative metabolism under stress19 that lead to the regulated release of purine and pyrimidine nucleotides like ATP and UTP through cell membrane channels 20. Inside the cell, ATP is an energy carrier.…”

Section: Introductionmentioning

confidence: 99%

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

Naviaux

Curtis

et al. 2017

Ann Clin Transl Neurol

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ObjectiveNo drug is yet approved to treat the core symptoms of autism spectrum disorder (ASD). Low‐dose suramin was effective in the maternal immune activation and Fragile X mouse models of ASD. The Suramin Autism Treatment‐1 (SAT‐1) trial was a double‐blind, placebo‐controlled, translational pilot study to examine the safety and activity of low‐dose suramin in children with ASD.MethodsTen male subjects with ASD, ages 5–14 years, were matched by age, IQ, and autism severity into five pairs, then randomized to receive a single, intravenous infusion of suramin (20 mg/kg) or saline. The primary outcomes were ADOS‐2 comparison scores and Expressive One‐Word Picture Vocabulary Test (EOWPVT). Secondary outcomes were the aberrant behavior checklist, autism treatment evaluation checklist, repetitive behavior questionnaire, and clinical global impression questionnaire.ResultsBlood levels of suramin were 12 ± 1.5 μmol/L (mean ± SD) at 2 days and 1.5 ± 0.5 μmol/L after 6 weeks. The terminal half‐life was 14.7 ± 0.7 days. A self‐limited, asymptomatic rash was seen, but there were no serious adverse events. ADOS‐2 comparison scores improved by −1.6 ± 0.55 points (n = 5; 95% CI = −2.3 to −0.9; Cohen's d = 2.9; P = 0.0028) in the suramin group and did not change in the placebo group. EOWPVT scores did not change. Secondary outcomes also showed improvements in language, social interaction, and decreased restricted or repetitive behaviors.InterpretationThe safety and activity of low‐dose suramin showed promise as a novel approach to treatment of ASD in this small study.

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“…[5][6][7] Much recent interest has focused on the role of ROS in normal and malignant cell biology. 8,9 Organisms living in aerobic conditions are continuously subjected to ROS, and the response to ROS influences central cellular processes such as proliferation, apoptosis, and senescence, and elevated levels of ROS are associated with various human diseases including various cancers. 10 Of note, Notch1 contributes to leukemia-initiating cells' maintenance through regulation of ROS intracellular levels.…”

Section: Introductionmentioning

confidence: 99%

Loss of Notch1-dependent p21^Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis

et al. 2014

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Oxidative Shielding or Oxidative Stress?

Cited by 124 publications

References 74 publications

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

Loss of Notch1-dependent p21^Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis

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Oxidative Shielding or Oxidative Stress?

Cited by 124 publications

References 74 publications

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

Loss of Notch1-dependent p21Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis

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Product

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Loss of Notch1-dependent p21^Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis