ABSTRACT
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-1ß. 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.
ABSTRACT
This study aimed to evaluate the effect of the preemptive administration of amantadine on postoperative analgesia in cats undergoing ovariohysterectomy and its influence on the physiological parameters. Twenty healthy domestic cats scheduled to undergo ovariohysterectomy at the Santa Cruz State University, Ilhéus, were divided into two groups: the control group (Group C; n = 10) and the amantadine group (Group A; n = 10). The cats in Group C received placebo capsules 30 min prior to the standard anesthetic protocol, whereas those in Group A received 5 mg/kg of amantadine orally 30 min prior to the standard anesthetic protocol. Postoperative pain was assessed using the visual analog scale and the UNESP-Botucatu multidimensional scale for the evaluation of postoperative pain in cats. The administration of amantadine had no effect on the physiological parameters evaluated. The pain scores in Group A were lower than those in Group C, indicating that the frequency of rescue analgesic administration cats in Group A was lower. That way, preemptive oral administration of amantadine at a dose of 5 mg/kg was effective at controlling postoperative pain in cats undergoing ovariohysterectomy. Moreover, no adverse effects or alterations in the physiological patterns were observed in the treated animals.
ABSTRACT
The Kisspeptin/Kiss1r system has been studied in mammalian ovaries. However, there are still no studies on the modulation of this system and its relationship with angiogenic and immunological mediators in the ovary of domestic cats, especially during pregnancy. We evaluated the expression of Kisspeptin/Kiss1r and angiogenic and immunological mediators during folliculogenesis, luteogenesis and luteal regression of cyclic and pregnant cats. The ovary exhibited moderate to intense expression for Kiss1, VEGF, Flk-1, INFγ and MIF in oocytes and the follicular wall, while Kiss1r expression was low in granulosa cells. In these cells, there was also a greater expression of Kiss1, INFγ and MIF, mainly in secondary follicles, while tertiary and preovulatory follicles exhibited greater expression of VEGF and Flk-1 in this layer. In luteogenesis, Kiss1 immunostaining was higher in mature corpora lutea (MCL) of pregnant cats compared to vacuolated CL (VCL) and corpus albicans (CA). Pregnancy also increased the luteal gene expression of Kiss1 as well as Kiss1, Kiss1r, Flk-1, and MIF immunostaining in MCL, while reduced the area of VEGF expression in VCL and luteal mRNA expression of Mif when compared to non-pregnant animals. In addition, positive gene correlation between Kiss1r and Mif was observed in the CL. Kiss1, Kiss1r, Vegf and Mif expression were lower in the CA of cats in anestrus. These findings reveal that the expression of Kisspeptin/Kiss1r and angiogenic and immunological mediators, in the ovary of domestic cats, depend on the follicular and luteal stage, and the luteal expression of these mediators is influenced by pregnancy.