Evaluation of the Therapeutic Potential of Amantadine in a Vincristine-Induced Peripheral Neuropathy Model in Rats.

Autor: Drummond ISA; Department of Agricultural and Environmental Sciences, State University of Santa Cruz (UESC), Ilhéus 45662-900, BA, Brazil., de Oliveira JNS; Department of Agricultural and Environmental Sciences, State University of Santa Cruz (UESC), Ilhéus 45662-900, BA, Brazil., Niella RV; Department of Agricultural and Environmental Sciences, State University of Santa Cruz (UESC), Ilhéus 45662-900, BA, Brazil., Silva ÁJC; Department of Agricultural and Environmental Sciences, State University of Santa Cruz (UESC), Ilhéus 45662-900, BA, Brazil., de Oliveira IS; Department of Agricultural and Environmental Sciences, State University of Santa Cruz (UESC), Ilhéus 45662-900, BA, Brazil., de Souza SS; Department of Agricultural and Environmental Sciences, State University of Santa Cruz (UESC), Ilhéus 45662-900, BA, Brazil., da Costa Marques CS; Department of Agricultural and Environmental Sciences, State University of Santa Cruz (UESC), Ilhéus 45662-900, BA, Brazil., Corrêa JMX; Department of Agricultural and Environmental Sciences, State University of Santa Cruz (UESC), Ilhéus 45662-900, BA, Brazil., Silva JF; Department of Biological Sciences, State University of Santa Cruz (UESC), Ilhéus 45662-900, BA, Brazil., de Lavor MSL; Department of Agricultural and Environmental Sciences, State University of Santa Cruz (UESC), Ilhéus 45662-900, BA, Brazil.
Jazyk: angličtina
Zdroj: Animals : an open access journal from MDPI [Animals (Basel)] 2024 Jun 30; Vol. 14 (13). Date of Electronic Publication: 2024 Jun 30.
DOI: 10.3390/ani14131941
Abstrakt: This study aimed to evaluate the therapeutic potential of amantadine in a vincristine-induced peripheral neuropathy model in rats. Forty-eight male Wistar rats were used. The treated groups received oral amantadine at doses of 2, 5, 12, 25 and 50 mg/kg, with daily applications for 14 days. The mechanical paw withdrawal threshold was measured using a digital analgesimeter. Immunohistochemical analysis of IL-6, TNFα, MIP1α, IL-10, CX3CR1, CXCR4, SOD, CAT and GPx, and enzymatic activity analysis of CAT, SOD and GPx were performed, in addition to quantitative PCR of Grp78 , Chop , Ho1 , Perk , Bax , Bcl-xL , Casp 3 , Casp 9 , IL-6 , IL-10 , IL-18 and IL-1β . The results showed an increase in nociceptive thresholds in animals that received 25 mg/kg and 50 mg/kg amantadine. Immunohistochemistry showed a decrease in the immunostaining of IL-6, TNFα, MIP1α and CX3CR1, and an increase in IL-10. CAT and SOD showed an increase in both immunochemistry and enzymatic analysis. qPCR revealed a reduced expression of genes related to endoplasmic reticulum stress and regulation in the expression of immunological and apoptotic markers. Amantadine demonstrated antinociceptive, anti-inflammatory and antioxidant effects in the vincristine-induced peripheral neuropathy model in rats, suggesting that amantadine may be considered an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.
Databáze: MEDLINE