title: Detoxification of 6-hydroxydopamine-induced dopaminergic neurodegeneration by 5,5-dimethyl-1-pyrroline N-oxide, a radical trapper, in hemiparkinsonian rats.
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.
authors.affiliation: Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inden
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Takata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasui
authors.forename: Kanji
authors.initials: K
authors.lastname: Yoshimoto
authors.forename: Eishi
authors.initials: E
authors.lastname: Ashihara
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003497:Cyclic N-Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008297:Male; D001523:Mental Disorders / Q000139:chemically induced / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D016627:Oxidopamine / Q000009:adverse effects*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D017665:Hydroxyl Radical; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D016627:Oxidopamine; D007501:Iron; D014446:Tyrosine 3-Monooxygenase