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A novel azulenyl nitrone antioxidant protects against MPTP and 3-nitropropionic acid neurotoxicities.
Exp Neurol. 2005 Jan; 191(1):86-93.EN

Abstract

Oxidative stress plays an important role in neuronal death in neurodegenerative disorders such as Parkinson's disease (PD) and Huntington's disease (HD). Animal models of PD or HD, produced by administration of the mitochondrial toxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 3-nitropropionic acid (3NP), respectively, show increased free radical generation. Free radicals generated in biological systems can react with spin-trapping compounds, such as nitrones, to form stable adducts. In recent years, the utility of nitrones has moved beyond analytical applications and into the realm of neuroprotection as antioxidants in both brain ischemia and models of neurodegenerative diseases. In the present study, we administered a new nitrone antioxidant, stilbazulenyl nitrone (STAZN), with either MPTP or 3NP. STAZN attenuated MPTP-induced striatal dopamine depletion by 40% and showed a tendency to dose-dependent neuroprotection. STAZN dose-dependently protected against loss of tyrosine hydroxylase immunoreactive neurons in the substantia nigra pars compacta. STAZN reduced the striatal lesion volume caused by systemic 3NP administration from 44 +/- 9 to 20 +/- 6 mm(3). The lipid peroxidation marker, malondialdehyde(MDA), was significantly increased in the striatum, cortex, and cerebellum of rats after administration of 3NP. These increases were blocked by co-injection of STAZN. Our data provide further evidence that STAZN is a neuroprotective free radical spin trap, and suggest that the development of new antioxidants will broaden our therapeutic strategies for neurodegenerative diseases.

Authors+Show Affiliations

Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15589515

Citation

Yang, Lichuan, et al. "A Novel Azulenyl Nitrone Antioxidant Protects Against MPTP and 3-nitropropionic Acid Neurotoxicities." Experimental Neurology, vol. 191, no. 1, 2005, pp. 86-93.
Yang L, Calingasan NY, Chen J, et al. A novel azulenyl nitrone antioxidant protects against MPTP and 3-nitropropionic acid neurotoxicities. Exp Neurol. 2005;191(1):86-93.
Yang, L., Calingasan, N. Y., Chen, J., Ley, J. J., Becker, D. A., & Beal, M. F. (2005). A novel azulenyl nitrone antioxidant protects against MPTP and 3-nitropropionic acid neurotoxicities. Experimental Neurology, 191(1), 86-93.
Yang L, et al. A Novel Azulenyl Nitrone Antioxidant Protects Against MPTP and 3-nitropropionic Acid Neurotoxicities. Exp Neurol. 2005;191(1):86-93. PubMed PMID: 15589515.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel azulenyl nitrone antioxidant protects against MPTP and 3-nitropropionic acid neurotoxicities. AU - Yang,Lichuan, AU - Calingasan,Noel Y, AU - Chen,Junyu, AU - Ley,James J, AU - Becker,David A, AU - Beal,M Flint, PY - 2004/03/16/received PY - 2004/07/07/revised PY - 2004/07/12/accepted PY - 2004/12/14/pubmed PY - 2005/2/19/medline PY - 2004/12/14/entrez SP - 86 EP - 93 JF - Experimental neurology JO - Exp Neurol VL - 191 IS - 1 N2 - Oxidative stress plays an important role in neuronal death in neurodegenerative disorders such as Parkinson's disease (PD) and Huntington's disease (HD). Animal models of PD or HD, produced by administration of the mitochondrial toxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 3-nitropropionic acid (3NP), respectively, show increased free radical generation. Free radicals generated in biological systems can react with spin-trapping compounds, such as nitrones, to form stable adducts. In recent years, the utility of nitrones has moved beyond analytical applications and into the realm of neuroprotection as antioxidants in both brain ischemia and models of neurodegenerative diseases. In the present study, we administered a new nitrone antioxidant, stilbazulenyl nitrone (STAZN), with either MPTP or 3NP. STAZN attenuated MPTP-induced striatal dopamine depletion by 40% and showed a tendency to dose-dependent neuroprotection. STAZN dose-dependently protected against loss of tyrosine hydroxylase immunoreactive neurons in the substantia nigra pars compacta. STAZN reduced the striatal lesion volume caused by systemic 3NP administration from 44 +/- 9 to 20 +/- 6 mm(3). The lipid peroxidation marker, malondialdehyde(MDA), was significantly increased in the striatum, cortex, and cerebellum of rats after administration of 3NP. These increases were blocked by co-injection of STAZN. Our data provide further evidence that STAZN is a neuroprotective free radical spin trap, and suggest that the development of new antioxidants will broaden our therapeutic strategies for neurodegenerative diseases. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/15589515/A_novel_azulenyl_nitrone_antioxidant_protects_against_MPTP_and_3_nitropropionic_acid_neurotoxicities_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(04)00276-6 DB - PRIME DP - Unbound Medicine ER -