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Novel free radical spin traps protect against malonate and MPTP neurotoxicity.
Exp Neurol. 1999 May; 157(1):120-6.EN

Abstract

Both malonate and 1-methyl-4-phenyl-1,2,5,6 tetrahydropyridine (MPTP) are neurotoxins which cause energy depletion, secondary excitotoxicity, and free radical generation. Malonate is a reversible inhibitor of succinate dehydrogenase, while MPTP is metabolized to 1-methyl-4-phenylpyridinium, an inhibitor of mitochondrial complex I. We examined the effects of pretreatment with the cyclic nitrone free radical spin trap MDL 101,002 on malonate and MPTP neurotoxicity. MDL 101,002 produced dose-dependent neuroprotection against malonate-induced striatal lesions. MDL 101, 002 produced significant protection against MPTP induced depletions of dopamine and its metabolites. MDL 101,002 also significantly attenuated MPTP-induced increases in striatal 3-nitrotyrosine concentrations. The free radical spin trap tempol also produced significant protection against MPTP neurotoxicity. These findings provide further evidence that free radical spin traps produce neuroprotective effects in vivo and suggest that they may be useful in the treatment of neurodegenerative diseases.

Authors+Show Affiliations

Neurology Service, Massachusetts General Hospital, Harvard Medical School, 32 Fruit Street, Boston, Massachusetts 02114, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10222114

Citation

Matthews, R T., et al. "Novel Free Radical Spin Traps Protect Against Malonate and MPTP Neurotoxicity." Experimental Neurology, vol. 157, no. 1, 1999, pp. 120-6.
Matthews RT, Klivenyi P, Mueller G, et al. Novel free radical spin traps protect against malonate and MPTP neurotoxicity. Exp Neurol. 1999;157(1):120-6.
Matthews, R. T., Klivenyi, P., Mueller, G., Yang, L., Wermer, M., Thomas, C. E., & Beal, M. F. (1999). Novel free radical spin traps protect against malonate and MPTP neurotoxicity. Experimental Neurology, 157(1), 120-6.
Matthews RT, et al. Novel Free Radical Spin Traps Protect Against Malonate and MPTP Neurotoxicity. Exp Neurol. 1999;157(1):120-6. PubMed PMID: 10222114.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel free radical spin traps protect against malonate and MPTP neurotoxicity. AU - Matthews,R T, AU - Klivenyi,P, AU - Mueller,G, AU - Yang,L, AU - Wermer,M, AU - Thomas,C E, AU - Beal,M F, PY - 1999/5/1/pubmed PY - 1999/5/1/medline PY - 1999/5/1/entrez SP - 120 EP - 6 JF - Experimental neurology JO - Exp Neurol VL - 157 IS - 1 N2 - Both malonate and 1-methyl-4-phenyl-1,2,5,6 tetrahydropyridine (MPTP) are neurotoxins which cause energy depletion, secondary excitotoxicity, and free radical generation. Malonate is a reversible inhibitor of succinate dehydrogenase, while MPTP is metabolized to 1-methyl-4-phenylpyridinium, an inhibitor of mitochondrial complex I. We examined the effects of pretreatment with the cyclic nitrone free radical spin trap MDL 101,002 on malonate and MPTP neurotoxicity. MDL 101,002 produced dose-dependent neuroprotection against malonate-induced striatal lesions. MDL 101, 002 produced significant protection against MPTP induced depletions of dopamine and its metabolites. MDL 101,002 also significantly attenuated MPTP-induced increases in striatal 3-nitrotyrosine concentrations. The free radical spin trap tempol also produced significant protection against MPTP neurotoxicity. These findings provide further evidence that free radical spin traps produce neuroprotective effects in vivo and suggest that they may be useful in the treatment of neurodegenerative diseases. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/10222114/Novel_free_radical_spin_traps_protect_against_malonate_and_MPTP_neurotoxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(99)97045-0 DB - PRIME DP - Unbound Medicine ER -