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Femtomolar concentrations of dextromethorphan protect mesencephalic dopaminergic neurons from inflammatory damage.
FASEB J. 2005 Apr; 19(6):489-96.FJ

Abstract

Inflammation in the brain has increasingly been recognized to play an important role in the pathogenesis of several neurodegenerative disorders, including Parkinson's disease (PD). Progress in the search for effective therapeutic strategies that can halt this degenerative process remains limited. We previously showed that micromolar concentrations of dextromethorphan (DM), a major ingredient of widely used antitussive remedies, reduced the inflammation-mediated degeneration of dopaminergic neurons through the inhibition of microglial activation. In this study, we report that femto- and micromolar concentrations of DM (both pre- and post-treatment) showed equal efficacy in protecting lipopolysaccharide (LPS) -induced dopaminergic neuron death in midbrain neuron-glia cultures. Both concentrations of DM decreased LPS-induced release of nitric oxide, tumor necrosis factor-alpha, prostaglandin E2 and superoxide from microglia in comparable degrees. The important role of superoxide was demonstrated by DM's failure to show a neuroprotective effect in neuron-glia cultures from NADPH oxidase-deficient mice. These results suggest that the neuroprotective effect elicited by femtomolar concentrations of DM is mediated through the inhibition of LPS-induced proinflammatory factors, especially superoxide. These findings suggest a novel therapeutic concept of using "ultra-low" drug concentrations for the intervention of inflammation-related neurodegenerative diseases.

Authors+Show Affiliations

Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. guorongl@med.unc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15790998

Citation

Li, Guorong, et al. "Femtomolar Concentrations of Dextromethorphan Protect Mesencephalic Dopaminergic Neurons From Inflammatory Damage." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 19, no. 6, 2005, pp. 489-96.
Li G, Cui G, Tzeng NS, et al. Femtomolar concentrations of dextromethorphan protect mesencephalic dopaminergic neurons from inflammatory damage. FASEB J. 2005;19(6):489-96.
Li, G., Cui, G., Tzeng, N. S., Wei, S. J., Wang, T., Block, M. L., & Hong, J. S. (2005). Femtomolar concentrations of dextromethorphan protect mesencephalic dopaminergic neurons from inflammatory damage. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 19(6), 489-96.
Li G, et al. Femtomolar Concentrations of Dextromethorphan Protect Mesencephalic Dopaminergic Neurons From Inflammatory Damage. FASEB J. 2005;19(6):489-96. PubMed PMID: 15790998.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Femtomolar concentrations of dextromethorphan protect mesencephalic dopaminergic neurons from inflammatory damage. AU - Li,Guorong, AU - Cui,Gang, AU - Tzeng,Nian-Ssheng, AU - Wei,Sung-Jen, AU - Wang,Tongguang, AU - Block,Michelle L, AU - Hong,Jau-Shyong, PY - 2005/3/26/pubmed PY - 2005/12/15/medline PY - 2005/3/26/entrez SP - 489 EP - 96 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J VL - 19 IS - 6 N2 - Inflammation in the brain has increasingly been recognized to play an important role in the pathogenesis of several neurodegenerative disorders, including Parkinson's disease (PD). Progress in the search for effective therapeutic strategies that can halt this degenerative process remains limited. We previously showed that micromolar concentrations of dextromethorphan (DM), a major ingredient of widely used antitussive remedies, reduced the inflammation-mediated degeneration of dopaminergic neurons through the inhibition of microglial activation. In this study, we report that femto- and micromolar concentrations of DM (both pre- and post-treatment) showed equal efficacy in protecting lipopolysaccharide (LPS) -induced dopaminergic neuron death in midbrain neuron-glia cultures. Both concentrations of DM decreased LPS-induced release of nitric oxide, tumor necrosis factor-alpha, prostaglandin E2 and superoxide from microglia in comparable degrees. The important role of superoxide was demonstrated by DM's failure to show a neuroprotective effect in neuron-glia cultures from NADPH oxidase-deficient mice. These results suggest that the neuroprotective effect elicited by femtomolar concentrations of DM is mediated through the inhibition of LPS-induced proinflammatory factors, especially superoxide. These findings suggest a novel therapeutic concept of using "ultra-low" drug concentrations for the intervention of inflammation-related neurodegenerative diseases. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/15790998/Femtomolar_concentrations_of_dextromethorphan_protect_mesencephalic_dopaminergic_neurons_from_inflammatory_damage_ L2 - https://doi.org/10.1096/fj.04-2555com DB - PRIME DP - Unbound Medicine ER -