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Combined minocycline plus pyruvate treatment enhances effects of each agent to inhibit inflammation, oxidative damage, and neuronal loss in an excitotoxic animal model of Huntington's disease.
Neuroscience. 2006 Sep 15; 141(4):1835-48.N

Abstract

The combination effects of minocycline (MC), a second-generation tetracycline compound and pyruvate (PY), a glycolysis end metabolite with antioxidant activity were investigated in the rat striatum following an excitotoxic insult. Striatal injection of quinolinic acid (QUIN) resulted in marked inflammation characterized by microgliosis, astrogliosis and enhanced expressions of pro-inflammatory enzymes inducible nitric oxide synthase and cyclooxygenase-2. Inflammatory responses were attenuated with administration of either MC or PY, however, the combination of both compounds was significantly more effective in reducing inflammation relative to MC or PY applied alone. Immunohistochemical analysis at 7 days post-intrastriatal QUIN injection showed extensive oxidative stress evident as lipid peroxidation, oxidative DNA damage and reactive oxygen species formation which was partially decreased by each agent applied separately but markedly inhibited with the combination of the two compounds. In addition, combination treatments significantly reduced neuronal loss in QUIN-injected striatum compared with the agents applied separately. Furthermore, long-term combination treatment decreased striatal lesions and inflammation after QUIN injection. These results demonstrate that MC and PY confer a considerably enhanced anti-inflammatory and neuroprotective efficacy when applied together and suggest this combinatorial procedure as a novel therapeutic strategy in neurodegenerative disorders such as Huntington's disease which exhibit excitotoxic insults.

Authors+Show Affiliations

Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, 2176 Health Sciences Mall, The University of British Columbia, Vancouver, BC, Canada V6T 1Z3.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16809003

Citation

Ryu, J K., et al. "Combined Minocycline Plus Pyruvate Treatment Enhances Effects of Each Agent to Inhibit Inflammation, Oxidative Damage, and Neuronal Loss in an Excitotoxic Animal Model of Huntington's Disease." Neuroscience, vol. 141, no. 4, 2006, pp. 1835-48.
Ryu JK, Choi HB, McLarnon JG. Combined minocycline plus pyruvate treatment enhances effects of each agent to inhibit inflammation, oxidative damage, and neuronal loss in an excitotoxic animal model of Huntington's disease. Neuroscience. 2006;141(4):1835-48.
Ryu, J. K., Choi, H. B., & McLarnon, J. G. (2006). Combined minocycline plus pyruvate treatment enhances effects of each agent to inhibit inflammation, oxidative damage, and neuronal loss in an excitotoxic animal model of Huntington's disease. Neuroscience, 141(4), 1835-48.
Ryu JK, Choi HB, McLarnon JG. Combined Minocycline Plus Pyruvate Treatment Enhances Effects of Each Agent to Inhibit Inflammation, Oxidative Damage, and Neuronal Loss in an Excitotoxic Animal Model of Huntington's Disease. Neuroscience. 2006 Sep 15;141(4):1835-48. PubMed PMID: 16809003.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combined minocycline plus pyruvate treatment enhances effects of each agent to inhibit inflammation, oxidative damage, and neuronal loss in an excitotoxic animal model of Huntington's disease. AU - Ryu,J K, AU - Choi,H B, AU - McLarnon,J G, Y1 - 2006/06/30/ PY - 2005/12/22/received PY - 2006/05/03/revised PY - 2006/05/18/accepted PY - 2006/7/1/pubmed PY - 2006/12/9/medline PY - 2006/7/1/entrez SP - 1835 EP - 48 JF - Neuroscience JO - Neuroscience VL - 141 IS - 4 N2 - The combination effects of minocycline (MC), a second-generation tetracycline compound and pyruvate (PY), a glycolysis end metabolite with antioxidant activity were investigated in the rat striatum following an excitotoxic insult. Striatal injection of quinolinic acid (QUIN) resulted in marked inflammation characterized by microgliosis, astrogliosis and enhanced expressions of pro-inflammatory enzymes inducible nitric oxide synthase and cyclooxygenase-2. Inflammatory responses were attenuated with administration of either MC or PY, however, the combination of both compounds was significantly more effective in reducing inflammation relative to MC or PY applied alone. Immunohistochemical analysis at 7 days post-intrastriatal QUIN injection showed extensive oxidative stress evident as lipid peroxidation, oxidative DNA damage and reactive oxygen species formation which was partially decreased by each agent applied separately but markedly inhibited with the combination of the two compounds. In addition, combination treatments significantly reduced neuronal loss in QUIN-injected striatum compared with the agents applied separately. Furthermore, long-term combination treatment decreased striatal lesions and inflammation after QUIN injection. These results demonstrate that MC and PY confer a considerably enhanced anti-inflammatory and neuroprotective efficacy when applied together and suggest this combinatorial procedure as a novel therapeutic strategy in neurodegenerative disorders such as Huntington's disease which exhibit excitotoxic insults. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/16809003/Combined_minocycline_plus_pyruvate_treatment_enhances_effects_of_each_agent_to_inhibit_inflammation_oxidative_damage_and_neuronal_loss_in_an_excitotoxic_animal_model_of_Huntington's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(06)00734-2 DB - PRIME DP - Unbound Medicine ER -