Oxidopamine hydrochloride (6-Hydroxydopamine hydrochloride)
(Synonyms: 6-羟基多巴胺盐酸盐; 6-Hydroxydopamine hydrochloride; 6-OHDA hydrochloride) 目录号 : GC30871
Oxidopamine hydrochloride (6-Hydroxydopamine hydrochloride)（6-OHDA）是神经递质多巴胺的拮抗剂。
Cas No.:28094-15-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >97.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
PC12 cells |
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Preparation Method |
PC12 cells(2×105cells/ml) were stained with Hoechst33342 after incubation for 24h with 0-150μM Oxidopamine hydrochloride and observed under fluorescence microscopy. |
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Reaction Conditions |
0-150µM; 24h |
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Applications |
Oxidopamine hydrochloride induces chromatin condensation in PC12 cells in a dose- and time-dependent manner. |
| Animal experiment [2]: | |
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Animal models |
Young adult (10 weeks old) and aged (17 months old) Wistar–Han female rats |
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Preparation Method |
Before the surgical procedure, animals were intraperitoneally anesthetized with ketamine-medetomidine. Subsequently, both young adult and aged rats were positioned on a stereotaxic frame and unilaterally injected in the right hemisphere with 2µL of Oxidopamine hydrochloride hydrochloride using a 30-gauge needle Hamilton syringe. Oxidopamine hydrochloride was administrated at a rate of 1.0µL/min at a concentration of 4µg/µL dissolved in 0.9% NaCl with 0.2mg/mL of ascorbic acid . The neurotoxin was injected into the Medial forebrain bundle（MFB）. |
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Dosage form |
8μg in 2μL saline; injected into the Medial forebrain bundle（MFB） |
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Applications |
Both old and young adult animals injected with Oxidopamine hydrochloride showed significant impairments in contralateral forelimb reaching test and forced choice task, and significant reductions in TH-expressing cells in the substantia nigra pars compacta (SNpc) and striatum. |
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References: |
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Oxidopamine hydrochloride (6-Hydroxydopamine hydrochloride) (6-OHDA) is an antagonist of the neurotransmitter dopamine[1]. Oxidopamine hydrochloride is a widely used neurotoxin that selectively destroys dopaminergic neurons[2]. Oxidopamine hydrochloride is often used to induce animal models of Parkinson's disease (PD)[3].
In vitro, 24h treatment of PC12 cells with Oxidopamine hydrochloride (0-150µM) induced chromatin condensation in a concentration- and time-dependent manner, increased the activity of caspase-3, -8, and -9 in cells, and depolarized the mitochondrial membrane[4]. 24h treatment of Neuro-2a and SH-SY5Y cells with Oxidopamine hydrochloride (0-500µM) reduced the viability of both cells in a concentration-dependent manner, with similar EC50 values(approximately 110µM), and induced cyclooxygenase-2 (COX-2) expression and nuclear translocation[5].
In vivo, Oxidopamine hydrochloride (8μg in 2μL saline) was injected into the medial forebrain bundle in old and young rats, which showed significant impairment in the contralateral forelimb reaching test and forced choice task, and a significant decrease in TH-expressing cells in the substantia nigra pars compacta (SNpc) and striatum[6]. Oxidopamine hydrochloride (5μg in 2μL saline) was injected unilaterally into the right striatum in SD rats, which induced nigrostriatal nerve terminal lesions, reduced striatal dopamine levels, and reduced the number of tyrosine hydroxylase immunoreactive cells in the ipsilateral substantia nigra, accompanied by significant atrophy of the remaining dopaminergic neurons[7].
References:
[1] De Boer P, Damsma G, Schram Q, et al. The effect of intrastriatal application of directly and indirectly acting dopamine agonists and antagonists on the in vivo release of acetylcholine measured by brain microdialysis: the importance of the post-surgery interval[J]. Naunyn-Schmiedeberg's archives of pharmacology, 1992, 345: 144-152.
[2] Pantic I, Cumic J, Skodric S R, et al. Oxidopamine and oxidative stress: Recent advances in experimental physiology and pharmacology[J]. Chemico-biological interactions, 2021, 336: 109380.
[3] Torres E M, Dunnett S B. 6-OHDA lesion models of Parkinson’s disease in the rat[J]. Animal Models of Movement Disorders: Volume I, 2012: 267-279.
[4] Fujita H, Ogino T, Kobuchi H, et al. Cell-permeable cAMP analog suppresses 6-hydroxydopamine-induced apoptosis in PC12 cells through the activation of the Akt pathway[J]. Brain research, 2006, 1113(1): 10-23.
[5] Kang X, Qiu J, Li Q, et al. Cyclooxygenase-2 contributes to oxidopamine-mediated neuronal inflammation and injury via the prostaglandin E2 receptor EP2 subtype[J]. Scientific reports, 2017, 7(1): 9459.
[6] Barata-Antunes S, Teixeira F G, Mendes-Pinheiro B, et al. Impact of aging on the 6-OHDA-induced rat model of Parkinson’s disease[J]. International journal of molecular sciences, 2020, 21(10): 3459.
[7] Jin F, Wu Q, Lu Y F, et al. Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson's disease in rats[J]. European journal of pharmacology, 2008, 600(1-3): 78-82.
Oxidopamine hydrochloride (6-Hydroxydopamine hydrochloride)（6-OHDA）是神经递质多巴胺的拮抗剂[1]。Oxidopamine hydrochloride是一种广泛应用的神经毒素，可选择性破坏多巴胺能神经元[2]。Oxidopamine hydrochloride常用于诱导帕金森病（PD）动物模型[3]。
在体外，Oxidopamine hydrochloride（0-150µM）处理PC12细胞24h，以浓度和时间依赖的方式诱导了细胞染色质凝聚，增加了细胞中caspase-3、-8和-9的活性，使线粒体膜去极化[4]。Oxidopamine hydrochloride（0-500µM）处理Neuro-2a和SH-SY5Y细胞24h，以浓度依赖的方式降低了两种细胞的活力，具有相似的EC50值（约110µM），诱导环氧合酶-2（COX-2）表达和核转位[5]。
在体内，Oxidopamine hydrochloride（8μg in 2μL saline）通过注射至内侧前脑束处理老年和年轻大鼠，在对侧前肢伸手测试和强制选择任务中均表现出明显障碍，并且黑质致密部（SNpc）和纹状体中TH表达细胞明显减少[6]。Oxidopamine hydrochloride（5μg in 2μL saline）通过单侧注入右侧纹状体处理SD大鼠，诱导了黑质纹状体神经末梢病变，降低了纹状体多巴胺水平，减少了同侧黑质中酪氨酸羟化酶免疫反应性细胞数量，并伴有剩余多巴胺能神经元的显著萎缩[7]。
| Cas No. | 28094-15-7 | SDF | |
| 别名 | 6-羟基多巴胺盐酸盐; 6-Hydroxydopamine hydrochloride; 6-OHDA hydrochloride | ||
| Canonical SMILES | OC1=CC(CCN)=C(O)C=C1O.[H]Cl | ||
| 分子式 | C8H12ClNO3 | 分子量 | 205.64 |
| 溶解度 | DMSO : ≥ 32 mg/mL (155.61 mM) | 储存条件 | Store at -20°C,unstable in solution, ready to use. |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.8629 mL | 24.3143 mL | 48.6287 mL |
| 5 mM | 0.9726 mL | 4.8629 mL | 9.7257 mL |
| 10 mM | 0.4863 mL | 2.4314 mL | 4.8629 mL |
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动物平均体重 | g | |
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动物数量 | 只 |
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6-Hydroxydopamine upregulates iron regulatory protein 1 by activating certain protein kinase C isoforms in the dopaminergic MES23.5 cell line
Iron-induced oxidative stress is thought to play a crucial role in the pathogenesis of Parkinson's disease. Our previous studies demonstrated that decreased expression of ferroportin 1 contributes to 6-hydroxydopamine induced intracellular iron accumulation and that decreased ferroportin 1 expression is caused by increased expression of iron regulatory protein 1. Iron regulatory protein 1 is a central regulator of iron homeostasis and is a likely target of extracellular agents to program changes in cellular iron metabolism. Therefore, the mechanism of iron regulatory protein 1 upregulation induced by 6-hydroxydopamine has become a significant focus of research. Iron regulatory protein 1 is regulated by protein kinase C, although this regulation is tissue specific. Therefore, in the present study, we aimed to determine whether alteration of protein kinase C activity modified iron regulatory protein 1 expression in the dopaminergic MES23.5 cell line, Furthermore, we investigated whether 6-hydroxydopamine induced iron regulatory protein 1 upregulation is mediated by protein kinase C, thus achieving regulation of cellular iron levels. The results showed that iron regulatory protein 1 was upregulated by phorbol 12-myristate-13-acetate, the PKC activator in dopaminergic MES23.5 cells, and ferroportin 1 expression and iron efflux were decreased as a result of iron regulatory protein 1 upregulation. The protein kinase C inhibitor bisindolylmaleimide I hydrochloride abolished the effect of phorbol 12-myristate-13-acetate. Protein kinase C-汛 and protein kinase C-汎, but not protein kinase C-? were activated by 6-hydroxydopamine. The protein kinase C-汛 inhibitor rottlerin inhibited protein kinase C-汛 phosphorylation and abolished iron regulatory protein 1 upregulation induced by 6-hydroxydopamine. The protein kinase C-汎 pseudo-substrate inhibitor inhibited protein kinase C-汎 phosphorylation and abolished iron regulatory protein 1 upregulation induced by 6-hydroxydopamine. These data indicate that iron regulatory protein 1 is regulated by protein kinase C in dopaminergic MES23.5 cells and that protein kinase C activated by 6-hydroxydopamine regulates iron regulatory protein 1 expression, thus achieving regulation of cellular iron levels.
Investigation of 6-hydroxydopamine-induced plasma extravasation in rat skin
Perfusion of 6-hydroxydopamine into the rat knee and trachea induces plasma extravasation, possibly by tissue-specific mechanisms involving sympathetic and sensory nerves respectively, and we aimed to identify the mediators which contribute to this response in skin. 6-Hydroxydopamine (both hydrobromide and hydrochloride salts), dose dependently increased plasma extravasation into rat dorsal skin, however, when compared to bradykinin or the tachykinin NK1 receptor agonist GR73632, high concentrations of 6-hydroxydopamine (1-10 mumol/site) were required. The response to 6-hydroxydopamine was not inhibited in chemically sympathectomised rats (6-hydroxydopamine, 300 mg/kg i.p. over 7 days) but was significantly reduced by co-administration with the histamine (H1) and the 5-HT receptor antagonists mepyramine and methysergide and in skin sites pre-injected with compound 48/80 (4 micrograms, -18 h) to degranulate dermal mast cells. The response was not inhibited by co-injection of the tachykinin NK1 receptor antagonist SRI40333 or by the cyclo-oxygenase inhibitor indomethacin (5 mg kg-1 i.p., -30 min) except at the lowest dose of 6-hydroxydopamine (1 mumol/site). We conclude that 6-hydroxydopamine is not a potent or selective mediator of increased vascular permeability in rat skin but, at high concentrations, may induce oedema formation via release of vasoactive amines from mast cells, augmented by generation of prostaglandins.
Effect of Roucongrong (Herba Cistanches Deserticolae) decoction on the substantia nigra through Wnt/汕-catenin signaling pathway in rats with Parkinson's disease induced by 6-hydroxydopamine hydrochloride
Objective: To investigate the effect of Roucongrong (Herba Cistanches Deserticolae) decoction on the substantia nigra in rats with Parkinson's disease (PD) induced by 6-hydroxydopamine hydrochloride (6-OHDA). To further determine whether the Wnt/汕-catenin signaling pathway is involved in the action.
Methods: A rat model of PD was established by intracranial injection of 6-OHDA. Subsequently, three concentrations of Roucongrong (Herba Cistanches Deserticolae) decoction were prepared and administered to rats by gavage therapy for 14 d. Behavioral changes were measured in PD rats. In vivo tyrosine hydroxylase (TH) levels in the substantia nigra were examined by immunohistochemistry. Additionally, gene and protein expression levels of members of the Wnt/汕-catenin signaling pathway were examined by Western blotting and polymerase chain reaction. Lastly, a Wnt/汕-catenin inhibitor was used to investigate the mechanism of action in 1-methyl-4-phenylpyridinium (MPP + )- treated MES23.5 cells in vitro.
Results: Roucongrong (Herba Cistanches Deserticolae) decoction improved performance in the stride and gait adjustment tests in PD rats. It also increased TH in the substantia nigra and altered the expression of genes and proteins in the Wnt/汕-catenin signaling pathway. Wnt/汕-catenin inhibitor reduced the effect of Roucongrong (Herba Cistanches Deserticolae) decoction in MPP +-treated MES23.5 cells.
Conclusion: Roucongrong (Herba Cistanches Deserticolae) decoction may promote neuronal survival in PD in vivo and in vitro by increasing TH content in the substantia nigra and by activating the Wnt/汕-catenin signaling pathway.
Nitroxide Radical-Containing Redox Nanoparticles Protect Neuroblastoma SH-SY5Y Cells against 6-Hydroxydopamine Toxicity
Parkinson's disease (PD) patients can benefit from antioxidant supplementation, and new efficient antioxidants are needed. The aim of this study was to evaluate the protective effect of selected nitroxide-containing redox nanoparticles (NRNPs) in a cellular model of PD. Antioxidant properties of NRNPs were studied in cell-free systems by protection of dihydrorhodamine 123 against oxidation by 3-morpholino-sydnonimine and protection of fluorescein against bleaching by 2,2-azobis(2-amidinopropane) hydrochloride and sodium hypochlorite. Model blood-brain barrier penetration was studied using hCMEC/D3 cells. Human neuroblastoma SH-SY5Y cells, exposed to 6-hydroxydopamine (6-OHDA), were used as an in vitro model of PD. Cells were preexposed to NRNPs or free nitroxides (TEMPO or 4-amino-TEMPO) for 2 h and treated with 6-OHDA for 1 h and 24 h. The reactive oxygen species (ROS) level was estimated with dihydroethidine 123 and Fluorimetric Mitochondrial Superoxide Activity Assay Kit. Glutathione level (GSH) was measured with ortho-phtalaldehyde, ATP by luminometry, changes in mitochondrial membrane potential with JC-1, and mitochondrial mass with 10-Nonyl-Acridine Orange. NRNP1, TEMPO, and 4-amino-TEMPO (25-150 米M) protected SH-SY5Y cells from 6-OHDA-induced viability loss; the protection was much higher for NRNP1 than for free nitroxides. NRNP1 were better antioxidants in vitro and permeated better the model BBB than free nitroxides. Exposure to 6-OHDA decreased the GSH level after 1 h and increased it considerably after 24 h (apparently a compensatory overresponse); NRNPs and free nitroxides prevented this increase. NRNP1 and free nitroxides prevented the decrease in ATP level after 1 h and increased it after 24 h. 6-OHDA increased the intracellular ROS level and mitochondrial superoxide level. Studied antioxidants mostly decreased ROS and superoxide levels. 6-OHDA decreased the mitochondrial potential and mitochondrial mass; both effects were prevented by NRNP1 and nitroxides. These results suggest that the mitochondria are the main site of 6-OHDA-induced cellular damage and demonstrate a protective effect of NRNP1 in a cellular model of PD.
Exercise attenuates levodopa-induced dyskinesia in 6-hydroxydopamine-lesioned mice
L-DOPA alleviates the motor symptoms of Parkinson's disease, but its long-term use is associated with undesirable dyskinesia. We now tested whether exercise can attenuate this L-DOPA-induced dyskinesia (LID). We tested the effects of exercise on LID in 6-hydroxydopamine hydrochloride-hemiparkinsonian mice. Animals were treated with L-DOPA/benserazide (25/12.5 mg/kg, i.p.) without and with possibility to exercise (running wheel) during 2 weeks. Exercise drastically prevented the development of LID, and its associated aberrant striatal signaling, namely the hyperphosphorylation of dopamine and cAMP-regulated phosphoprotein 32 kDa protein and c-Fos expression. Our results indicate that exercise can partially prevent the development of LID through the normalization of striatopallidal dopaminergic signaling.