Oral administration of carvacrol/β-cyclodextrin complex protects against 6-hydroxydopamine-induced dopaminergic denervation
| Autor: | Daniel Oppermann Peixoto, Juciano Gasparotto, Roberto Farina de Almeida, Alice Kunzler, Rafael Calixto Bortolin, Adriano Antunes de Souza Araújo, Pedro Ozorio Brum, Lucindo José Quintans-Júnior, Helen Tais da Rosa Silva, Daniel Pens Gelain, José Cláudio Fonseca Moreira, Lyvia Lintzmaier Petiz, Camila Tiefensee Ribeiro |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Antioxidant medicine.medical_treatment Administration Oral Pharmacology Neuroprotection 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Oral administration medicine Animals Carvacrol Rats Wistar Oxidopamine Denervation Hydroxydopamine Chemistry Dopaminergic Neurons beta-Cyclodextrins Dopaminergic Cell Biology Rats Bioavailability Drug Combinations Oxidative Stress Neuroprotective Agents 030104 developmental biology Cymenes 030217 neurology & neurosurgery |
| Zdroj: | Neurochemistry International. 126:27-35 |
| ISSN: | 0197-0186 |
| DOI: | 10.1016/j.neuint.2019.02.021 |
| Popis: | Carvacrol (CARV) presents valuable biological properties such as anti-inflammatory and antioxidant activities. However, pharmacological uses of CARV are largely limited due to disadvantages related to solubility, bioavailability, preparation and storage processes. The complexation of monoterpenes with β-cyclodextrin (β-CD) increases their stability, solubility and oral bioavailability. Here, the protective effect of oral treatment with CARV/β-CD complex (25 μg/kg/day) against dopaminergic (DA) denervation induced by unilateral intranigral injection of 6-hydroxydopamine (6-OHDA - 10 μg per rat) was analyzed, in order to evaluate a putative application in the development of neuroprotective therapies for Parkinson's disease (PD). Pretreatment with CARV/β-CD for 15 days prevented the loss of DA neurons induced by 6-OHDA in adult Wistar rats. This effect may occur through CARV anti-inflammatory and antioxidant properties, as the pretreatment with CARV/β-CD inhibited the release of IL-1β and TNF-α; besides, CARV prevented the increase of mitochondrial superoxide production induced by 6-OHDA in cultured SH-SY5Y cells. Importantly, hepatotoxicity or alterations in blood cell profile were not observed with oral administration of CARV/β-CD. Therefore, this study showed a potential pharmacological application of CARV/β-CD in PD using a non-invasive route of drug delivery, i.e., oral administration. |
| Databáze: | OpenAIRE |
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