Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The administration of high doses of methamphetamine causes the degeneration of striatal dopaminergic fibers in the brains of rodents, and oxidative stress appears to be one of the main factors of neurotoxicity. This study examined whether edaravone, a radical scavenger, protects against methamphetamine-induced neurotoxicity in mice. Methamphetamine treatment (4 mg/kg, s.c. x 4 with 2 h intervals) showed striatal dopaminergic degeneration as observed by decreases in dopamine levels and tyrosine hydroxylase immunoreactivity in the striatum. The neurotoxicity was reduced by edaravone (3 mg/kg, i.p.), when it was administered four times 30 min before methamphetamine at 2 h intervals and additionally four times after methamphetamine at 12 h intervals. An immunohistochemical study showed that methamphetamine increased 3-nitrotyrosine immunoreactivity, an in vivo marker of peroxynitrite production, and activated microglia and astrocytes in the striatum. Edaravone blocked the increase in 3-nitrotyrosine immunoreactivity and the activation of astrocytes, but it did not affect the activation of microglia. Edaravone did not affect methamphetamine-induced hyperthermia and striatal dopamine release. These results suggest that edaravone protects against methamphetamine-induced neurotoxicity in the striatum by blocking peroxynitrite production. This study also suggests that methamphetamine activates microglia in a radical-independent mechanism.
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PMID:Protective effect of the radical scavenger edaravone against methamphetamine-induced dopaminergic neurotoxicity in mouse striatum. 1678 40

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity and behavioral impairment in rodents, and previous studies suggest that nitric oxide and reactive oxygen species are involved in MPTP-induced neurotoxicity. The present study examines the effect of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a radical scavenger, on MPTP-induced neurotoxicity in the striatum and substantia nigra pars compacta (SNc) of C57BL/6J mice. MPTP treatment (10 mg/kg s.c. x 4 with 2-h intervals) decreased dopamine levels and tyrosine hydroxylase immunostaining in the striatum and SNc. Pretreatment with edaravone (1 and 3 mg/kg i.p.) significantly reduced the neurotoxicity in the SNc but not striatum. An immunohistochemical study showed that MPTP caused microglial activation both in the striatum and SNc, whereas it increased 3-nitrotyrosine immunoreactivity, an in vivo biomarker of peroxynitrite production, in the SNc but not the striatum. Furthermore, MPTP increased lipid peroxidation product thiobarbituric acid reactive substance in the midbrain, but not the striatum. Edaravone inhibited activation of the microglia and the increased 3-nitrotyrosine immunoreactivity in the SNc but not the striatum, and it also inhibited thiobarbituric acid reactive substance levels in the midbrain. Behavioral analyses showed that edaravone improved MPTP-induced impairment of locomotion and Rotorod performance. These results suggest that edaravone protects against MPTP-induced neurotoxicity in the SNc by blocking the production of reactive oxygen species or peroxynitrite and imply that dopaminergic degeneration in the SNc may play an important role in MPTP-induced motor dysfunction of mice.
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PMID:Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a radical scavenger, prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in the substantia nigra but not the striatum. 1742 58

To investigate the mechanism of the neuroprotective effect of edaravone in substantia nigra (SN) of the 6-OHDA-induced rat model of Parkinson's disease. Animal model of Parkinson's disease was induced in male Sprague-Dawley rats by injecting 6-OHDA into the left medial forebrain bundle. Subsequently, rats were intraperitoneally injected with 0.3, 1, or 3 mg/kg of edaravone for 14 days or with 3 mg/kg edaravone for 14 days followed by 14 days of no treatment. We evaluated the effect of edaravone on the rotational and normal behavior of the rats, and on the number of tyrosine hydroxylase (TH)-positive cells, the amount of Nissl bodies, and the levels of glutathione (GSH), and malondialdehyde (MDA) in the SN. Edaravone treatment at 3 mg/kg significantly reduced apomorphine-induced rotational behavior (P < 0.01), improved the spontaneous behavior, prevented the decrease in the levels of TH-positive cells, Nissl bodies and GSH, and inhibited the increase in the levels of MDA (P < 0.05) in SN of rats with 6-OHDA-induced PD. Edaravone exerted a long-term neuroprotective effects in 6-OHDA-induced PD animal model by attenuating changes in the levels of GSH and MDA in SN, caused by oxidative stress. Edaravone prevented 6-OHDA-induced behavioral changes and de-pigmentation of SN that results from the loss of dopaminergic neurons.
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PMID:Edaravone protects neurons in the rat substantia nigra against 6-hydroxydopamine-induced oxidative stress damage. 2494 72