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

• DOI: 10.1016/j.neuint.2019.02.021
• Publication Date: 2019-03-05T07:11:53Z
• Authors: Camila Tiefensee ...; Juciano Gasparotto; Lyvia Lintzmaier ...; Pedro Ozorio Brum; Daniel Oppermann ...; Alice Kunzler; Helen Tais da Ros...; Rafael Calixto Bo...; Roberto Farina Al...; Lucindo José Quin...; Adriano Antunes A...; José Claudio Fons...; Daniel Pens Gelain
• Keywords: Male; 0301 basic medicine; Dopaminergic Neurons; beta-Cyclodextrins; Administration, Oral; Denervation; Rats; 3. Good health; Drug Combinations; Oxidative Stress; 03 medical and health sciences; Neuroprotective Agents; Animals; Cymenes; Rats, Wistar; Oxidopamine

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.