Dexmedetomidine attenuates the induction and reverses the progress of 6-hydroxydopamine- induced parkinsonism; involvement of KATP channels, alpha 2 adrenoceptors and anti-inflammatory mechanisms
| Autor: | Azita Minaei, Hashem Haghdoost-Yazdi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pharmacology Agonist endocrine system Hydroxydopamine business.industry medicine.drug_class Parkinsonism Antagonist Toxicology medicine.disease Neuroprotection Yohimbine Glibenclamide 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Dopamine 030220 oncology & carcinogenesis polycyclic compounds Medicine business hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Toxicology and Applied Pharmacology. 382:114743 |
| ISSN: | 0041-008X |
| Popis: | Background Studies have shown that dexmedetomidine (DEX), a potent α2-adrenoceptors agonist provides neuroprotection through suppression of inflammatory response. In present study, we examined effect of DEX and its underlying mechanisms on the induction and progress of 6-OHDA- induced Parkinsonism in rat. Material and methods The 6-OHDA was injected into the medial forebrain bundle of right hemisphere by stereotaxic surgery and then, behavioral tests carried out within second, fourth, sixth and eighth weeks post-surgery. All treatments were started before the toxin and continued to eight weeks afterwards. Striatal levels of dopamine, TNF-α and IL-6 were measured within the eighth week after the toxin by enzyme-linked immunosorbent assay kits. Results DEX at dose of 50 μg/kg attenuated significantly the intensity of 6-OHDA- induced behavioral symptoms in the second week post-surgery. DEX also attenuated remarkably 6-OHDA- induced reduction in striatal dopamine level. These effects were also observed in rats treated by both DEX and yohimbine (YOH), a selective α2-adrenoceptors antagonist but were not observed in rats treated by both of DEX and glibenclamide (Glib), an ATP-sensitive potassium (KATP) channels blocker. DEX also reversed the progressive increase in intensity of the behavioral symptoms and reversed 6-OHDA- induced overproduction of TNF-α and IL-6. These effects were reversed by YOH but not Glib. Conclusion Our findings indicate that DEX attenuates the induction and reverses the progress of 6-OHDA- induced Parkinsonism through activation of KATP channels and α2-adrenoceptors, respectively. Through activation of α2-adrenoceptors, DEX also exerts anti-inflammatory effect which is possibly another mechanism underlying the DEX's antiparkinsonism effect. |
| Databáze: | OpenAIRE |
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