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Detoxification of 6-hydroxydopamine-induced dopaminergic neurodegeneration by 5,5-dimethyl-1-pyrroline N-oxide, a radical trapper, in hemiparkinsonian rats.
- Source :
-
Biological & pharmaceutical bulletin [Biol Pharm Bull] 2012; Vol. 35 (9), pp. 1603-6. - Publication Year :
- 2012
-
Abstract
- Several useful spin trap agents have been identified for the identification and quantification of biological oxygen radicals. Among them, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) has been used most frequently as a spin trap agent. The function of DMPO in vivo, however, is still unclear. Thus, the purpose of this study was to evaluate the effect of DMPO in an in vivo model of Parkinson's disease (PD). Rats were microinjected with 6-hydroxydopamine (6-OHDA, 32 nmol) in the presence or absence of DMPO (0.4, 4 nmol). We investigated behavioral and histochemical parameters in this rat model of PD. In addition, to examine the effect of DMPO against oxidative stress, we performed an electron spin resonance (ESR) analysis. Intranigral injection of 6-OHDA alone caused behavioral dysfunction and a massive loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNpc). Co-microinjection of 4 nmol DMPO, but not 0.4 nmol, significantly prevented 6-OHDA-induced behavioral impairments and dopaminergic neurodegeneration. In ESR analysis, DMPO directly trapped hydroxyl radical (·OH) generated from 6-OHDA and Fe2+ in a concentration-dependent manner. These results suggest that DMPO attenuates 6-OHDA-induced dopaminergic neurodegeneration in a rat model of PD via scavenging ·OH, and is a useful tool for biological research of oxidative stresses.
- Subjects :
- Animals
Antioxidants therapeutic use
Behavior, Animal drug effects
Behavior, Animal physiology
Cyclic N-Oxides therapeutic use
Disease Models, Animal
Dose-Response Relationship, Drug
Hydroxyl Radical metabolism
Iron metabolism
Male
Mental Disorders chemically induced
Parkinson Disease drug therapy
Rats
Rats, Wistar
Substantia Nigra cytology
Substantia Nigra metabolism
Tyrosine 3-Monooxygenase metabolism
Antioxidants pharmacology
Cyclic N-Oxides pharmacology
Mental Disorders metabolism
Oxidative Stress drug effects
Oxidopamine adverse effects
Parkinson Disease metabolism
Substantia Nigra drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1347-5215
- Volume :
- 35
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Biological & pharmaceutical bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 22975516
- Full Text :
- https://doi.org/10.1248/bpb.b12-00300