Evaluation of the Therapeutic Potential of Amantadine in a Vincristine-Induced Peripheral Neuropathy Model in Rats
2024
Isabela Santana Albertazzi Drummond | Jéssica Natália Silva de Oliveira | Raquel Vieira Niella | Álvaro José Chávez Silva | Iago Santos de Oliveira | Sophia Saraiva de Souza | Claire Souza da Costa Marques | Janaina Maria Xavier Corrêa | Juneo Freitas Silva | Mário Sérgio Lima de Lavor
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 <i>Grp78</i>, <i>Chop</i>, <i>Ho1</i>, <i>Perk</i>, <i>Bax</i>, <i>Bcl-xL</i>, <i>Casp 3</i>, <i>Casp 9</i>, <i>IL-6</i>, <i>IL-10</i>, <i>IL-18</i> and <i>IL-1β</i>. 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.
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