Post-treatment with maropitant reduces oxidative stress, endoplasmic reticulum stress and neuroinflammation on peripheral nerve injury in rats.
PLoS One
; 19(3): e0287390, 2024.
Article
em En
| MEDLINE
| ID: mdl-38507417
ABSTRACT
OBJECTIVE:
To determine the effective dose and therapeutic potential of maropitant using through expression of mediators of oxidative stress, inflammatory and of the unfolded protein response (UPR) (bio) markers on spinal cord using a model of neuropathic pain induced through chronic constriction injury (CCI) in rats. STUDYDESIGN:
Randomized, blinded, prospective experimental study. ANIMALS 98 male Wistar rats.METHODS:
Rats were anesthetized with sevoflurane and after CCI, they were randomly assigned to the following groups that received vehicle, 3, 6, 15, 30 e 50 mg/kg/24q of maropitant. The effect on inflammatory mediators (IL10, TNFα), oxidative stress (GPx, CAT, SOD), microglial (IBA-1) and neuronal (NeuN, TACR1) markers was evaluated though immunohistochemistry and expression levels of markers of hypoxia (HIF1α, Nrf2), antioxidant enzymes (Catalse, Sod1 and GPx1), and endoplasmic reticulum stress mediators (GRP78, CHOP and PERK) through qRT-PCR.RESULTS:
Intraperitoneal injection (IP) of maropitant inhibited nociception with ID50 values of 4,1 mg/kg (5,85-19,36) in a neuropathic pain model through CCI. A dose of 30 mg/kg/24q was significantly effective in reducing mechanical allodynia 1 to 4h after treatment with nociception inhibition (145,83%). A reduction in the expression of hypoxia factors (HIF1α, Nrf2) was observed, along with an increase in antioxidant activity (CAT, SOD and GPX). Additionally, there was a reduction in inflammatory markes (IL10, TNFα), microglial (IBA-1), and neuronal markers (NeuN, TACR1). CONCLUSION AND CLINICAL RELEVANCE These findings demonstrate that the determined dose, administered daily for seven days, had an antinociceptive effect, as well as anti-inflammatory and antioxidant activity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinuclidinas
/
Traumatismos dos Nervos Periféricos
/
Neuralgia
Limite:
Animals
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Brasil