Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into the spinal cord in experimental autoimmune encephalomyelitis

Chaudhary, Poras; Marracci, Gail; Bourdette, Dennis

doi:10.1016/j.jneuroim.2006.03.007

Cited by 91 publications

(85 citation statements)

References 48 publications

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“…4). The same phenomenon was also found with ICAM-1, a well characterized adhesion molecule expressed on inflamed BBB endothelial cells (Alvarez et al, 2011;Chaudhary et al, 2006) (data not shown). These results suggest that treatment with AACOCF3 may preserve the BBB integrity in EAE mice.…”

Section: Aacocf3 Preserved the Integrity Of Blood-brain Barrier Aftersupporting

confidence: 72%

Arachidonyl trifluoromethyl ketone ameliorates experimental autoimmune encephalomyelitis via blocking peroxynitrite formation in mouse spinal cord white matter

Vana

Ribeiro

et al. 2011

Experimental Neurology

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Inhibition of phospholipase A 2 (PLA 2 ) has recently been found to attenuate the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of multiple sclerosis (MS). However, the protective mechanisms that underlie PLA 2 inhibition are still not well understood. In this study, we found that cytosolic PLA 2 (cPLA 2 ) was highly expressed in infiltrating lymphocytes and macrophages/microglia in mouse spinal cord white matter. Although cPLA 2 is also expressed in spinal cord neurons and oligodendrocytes, there were no differences observed in these cell types between EAE and control animals. Arachidonyl trifluoromethyl ketone (AACOCF3), a cPLA 2 inhibitor, significantly reduced the clinical symptoms and inhibited the body weight loss typically found in EAE mice. AACOCF3 also attenuated the loss of mature, myelin producing, oligodendrocytes, and axonal damage in the spinal cord white matter. Nitrotyrosine immunoreactivity, an indicator of peroxynitrite formation, was dramatically increased in EAE mice and attenuated by treatment with AACOCF3. These protective effects were not evident when AA861, an inhibitor of lipoxygenase, was used. In primary cultures of microglia, lipopolysaccharide (LPS) induced an upregulation of cPLA 2 , inducible nitric oxide synthase (iNOS) and components of the NADPH oxidase complex, p47phox and p67phox. AACOCF3 significantly attenuated iNOS induction, nitric oxide production and the generation of reactive oxygen species in reactive microglia. Similar to the decomposition catalyst of peroxynitrite, AACOCF3 also blocked oligodendrocyte toxicity induced by reactive microglia. These results suggest that AACOCF3 may prevent oligodendrocyte loss in EAE by attenuating peroxynitrite formation in the spinal cord white matter.Published by Elsevier Inc.

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Section: Aacocf3 Preserved the Integrity Of Blood-brain Barrier Aftersupporting

confidence: 72%

Arachidonyl trifluoromethyl ketone ameliorates experimental autoimmune encephalomyelitis via blocking peroxynitrite formation in mouse spinal cord white matter

Vana

Ribeiro

et al. 2011

Experimental Neurology

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“…The decreased expression of platelet endothelial cell adhesion molecule-1 played an important role in PQinduced lung injury. [13] LA could inhibit the generation of vascular cell adhesion molecules (VCAM-1) and intercellular adhesion molecule (ICAM-1), [14,15] alleviate the inflammation and vascular permeability, and reduce the level of TNF-α. LA could effectively suppress reactive oxygen species (ROS), and play an antioxidant effect.…”

Section: Discussionmentioning

confidence: 99%

Effect of SP-A/B in lipoic acid on acute paraquat poisoning

Han

Sun

et al. 2014

World Journal of Emergency Medicine

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BACKGROUND: This study was undertaken to observe the concentration of SP-A/B and the pulmonary surfactant in the lung tissue of rats with acute lung injury/acute respiratory distress syndrome caused by paraquat poisoning after the treatment of metabolic antioxidant-lipoic acid and whether its infl uence was related to TNF-α. METHODS:Sixty-six male Sprage-Dawley rats were randomly divided into three groups: normal control group (NS group), 6 rats; paraquat poisoning group (PQ group), 30 rats; and paraquat+lipoic acid treatment group (LA group), 30 rats. The rats in the PQ and LA groups were subdivided into 3-, 6-, 12-, 24-, 48-hour subgroups, with 6 rats in each group. After the rats were sacrifi ced, lung tissue from the same part was taken from the rats. After HE staining, histological changes were observed in the tissue under a light microscope. Lung tissue was also taken to test the levels of superoxide dismutase (SOD) and malondialdehyde (MDA). Whole blood (0.8 mL) without anticoagulant was drawn from the tail vein of rats for the determination of the TNF-α level. The total RNA of the lung tissue was collected, and the Rt-PCR method was used to measure the levels of SP-A and SP-B mRNA.RESULTS: HE staining showed that histopathological changes were milder in the LA group than in the PQ group. There were signifi cant differences in MDA and SOD levels between different intervals both in intergroups and intragroups except the 3-hour subgroup (P<0.01). Likewise, the significant differences in the levels of TNF-α were also present between the three groups and between different intervals (P<0.01). The significant differences in SP-A mRNA and SP-B mRNA amplification ratio were seen between the three groups at the same intervals (P<0.01), but the differences between different intervals in the PQ group were statistically significant (P<0.05). The differences between different intervals in the LA group were statistically signifi cant (P<0.01).CONCLUSION: Lipoic acid in acute paraquat poisoning could diminish lung tissue damage by regulating directly tumor necrosis factor and indirectly the content of pulmonary surfactant so as to reduce pulmonary edema, improve lung compliance, and fi nally protect lung tissues.

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“…[62][63][64][65] The remaining preclinical studies utilized the EAE rodent model. 42,62,[66][67][68][69][70][71] Detailed information is found in Supplementary Table 5 and risk-of-bias assessments in Supplementary Figure 4(a) and (b).…”

Section: Anti-oxidant Vitaminsmentioning

confidence: 99%

“…42 In five studies there was a consistent reduction in T cell infiltration into the CNS with ALA treatment: spinal cord, 42,67,69,71 optic nerve, 66 and cerebellum. 42,71 The six studies examining the effects of ALA on mediators of inflammation, such as matrix metallopedtidase-9 (MMP-9) or soluble cell adhesion molecule (ICAM), in animal models 42,67,70 and people with MS, 63,64,72 reported varying results. In serum obtained from people with MS, 1200 mg LA administered daily for 14 days did not change serum levels of MMP-9, TIMP-1, or soluble cell adhesion molecule (ICAM).…”

Section: Anti-oxidant Vitaminsmentioning

confidence: 99%

“…67 Two animal studies reported dosedependent effects of ALA, with higher dosages (100 µg/ml versus 25 µg/ml) being more beneficial and oral ingestion being less effective than injection. 67,70 Effects of ALA on recovery and repair were evaluated in two ways: quantification of demyelination and axonal injury, 66,69,70 and behavioral/clinical neurological impairment score. The three studies examining the effects of ALA on demyelination and axonal damage in optic nerve, spinal cord, and brain consistently showed that ALA-treated EAE animals had reduced damage in the CNS, 66,69,70 which was dependent on timing and route of administration.…”

Section: Anti-oxidant Vitaminsmentioning

confidence: 99%

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Over-the-counter anti-oxidant therapies for use in multiple sclerosis: A systematic review

et al. 2015

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Background: Anti-oxidant compounds that are found in over-the-counter (OTC) supplements and foods are gaining interest as treatments for multiple sclerosis (MS). They are widely used by patients, sometimes without a clear evidence base. Objective: We conducted a systematic review of animal and clinical research to determine the evidence for the benefits of OTC anti-oxidants in MS. Methods: Using predefined criteria, we searched key databases. Two authors scrutinized all studies against inclusion/exclusion criteria, assessed study risk-of-bias and extracted results. Results: Of the 3507 titles, 145 met criteria and included compounds, α(alpha)-lipoic acid (ALA), antioxidant vitamins, Ginkgo biloba, quercetin, resveratrol and epigallocatechin-3-gallate (ECGC). The strongest evidence to support OTC anti-oxidants was for compounds EGCG and ALA in animal models; both consistently showed anti-inflammatory/anti-oxidant effects and reduced neurological impairment. Only vitamin E, Ginkgo biloba and ALA were examined for efficacy in pilot clinical trials with either conflicting evidence or evidence of no benefit. Conclusion: OTC anti-oxidants EGCG and ALA show the most consistent benefit, however only in preclinical studies. There is no evidence that they alter MS relapses or progression. Future work should focus on testing more of these therapies for clinical efficacy before recommending them to MS patients. Anti-oxidant drug therapies, diets, and supplements, purported to counteract ROS and RNS cascades, are available as over-the-counter (OTC) remedies yet their benefits have not been proven. Most people with MS reporting using an OTC supplement despite the lack of a clear evidence base. 15 We undertook this study to systematically and rigorously examine current research findings on the effects of OTC anti-oxidant supplements in animal models and clinical trials in MS. Our aim was to translate research findings to MS clinicians and to identify areas for future research. Keywords Methods Search strategyWith the assistance of a librarian expert in systematic reviews and using predefined search terms (Table 1), we searched PubMed, CINAHL, PsychInfo, the Cochrane Library, and the Central Register of Controlled Clinical Trials, including all years up to 1 October 2013 (English language only). Clinical studies were included if the participants had MS or the biological products tested were from people with MS. Animal studies were included if a disease, similar to MS, was induced in animals and included at least behavioral findings. Data extraction and synthesisFollowing Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 16 and after duplicates were removed, we merged titles retrieved across search databases. At the title, abstract, and manuscript levels of the search, two authors evaluated inclusion status independently and if the authors disagreed, the article was included. Data extraction and synthesis was conducted on manuscripts that were categorized by compound tested. Referenc...

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Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into the spinal cord in experimental autoimmune encephalomyelitis

Cited by 91 publications

References 48 publications

Arachidonyl trifluoromethyl ketone ameliorates experimental autoimmune encephalomyelitis via blocking peroxynitrite formation in mouse spinal cord white matter

Arachidonyl trifluoromethyl ketone ameliorates experimental autoimmune encephalomyelitis via blocking peroxynitrite formation in mouse spinal cord white matter

Effect of SP-A/B in lipoic acid on acute paraquat poisoning

Over-the-counter anti-oxidant therapies for use in multiple sclerosis: A systematic review

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