Oral administration of carvacrol/β-cyclodextrin complex protects against 6-hydroxydopamine-induced dopaminergic denervation

• Published in: Neurochemistry international Vol. 126; pp. 27 - 35
• Main Authors: Tiefensee Ribeiro, Camila, Gasparotto, Juciano, Petiz, Lyvia Lintzmaier, Brum, Pedro Ozorio, Peixoto, Daniel Oppermann, Kunzler, Alice, da Rosa Silva, Helen Tais, Bortolin, Rafael Calixto, Almeida, Roberto Farina, Quintans-Junior, Lucindo José, Araújo, Adriano Antunes, Moreira, José Claudio Fonseca, Gelain, Daniel Pens
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2019
• Subjects: 6-hydroxydopamine; Administration, Oral; Animals; beta-Cyclodextrins - administration & dosage; Carvacrol; Cymenes - administration & dosage; Denervation - adverse effects; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - pathology; Drug Combinations; Male; Neuroprotective Agents - administration & dosage; Oxidative Stress - drug effects; Oxidative Stress - physiology; Oxidopamine - toxicity; Parkinson's disease; Rats; Rats, Wistar; β-cyclodextrin; Carvacrol; 6-hydroxydopamine; Parkinson's disease; β-cyclodextrin
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2019.02.021

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. •CARV/β-CD prevented the loss of DA neurons.•CARV/β-CD decreased the release of inflammatory mediators in CSF and serum.•CARV reduced the mitochondrial production of superoxide induced by 6-OHDA.•CARV/β-CD did not induce systemic toxicity.