Bottari Nathieli B, Baldissera Matheus D, Tonin Alexandre A, Rech Virginia C, Alves Catiane B, D'Avila Fernanda, Thomé Gustavo R, Guarda Naiara S, Moresco Rafael N, Camillo Giovana, Vogel Fernanda F, Luchese Cristiane, Schetinger Maria Rosa C, Morsch Vera M, Tochetto Camila, Fighera Rafael, Nishihira Vivian S K, Da Silva Aleksandro S
Graduate Program in Toxicological Biochemistry, Universidade Federal de Santa Maria (UFSM), RS, Brazil.
Programa de Pós-Graduação em Nanociências, Centro Universitário Franciscano, Santa Maria, RS, Brazil.
Microb Pathog. 2016 Jun;95:166-174. doi: 10.1016/j.micpath.2016.04.002. Epub 2016 Apr 4.
This study aimed to investigate the synergistic effects of resveratrol and sulfamethoxazole-trimethoprim (ST) on the treatment of mice experimentally infected by Toxoplasma gondii during the chronic phase of the disease considering infection, behavior, and oxidative/antioxidants profile aspects. For the study, 60 mice were initially divided into two groups: uninfected (n = 24) and infected by T. gondii (n = 36). These two groups were later subdivided into other groups and treated with resveratrol (free and inclusion complex containing resveratrol) alone and co-administered with ST: groups A to D were composed by healthy mice and groups E to J were consisted of animals infected by T. gondii (VEG strain). Treatments began 20 days post-infection for 10 consecutive days with oral doses of 0.5 mg kg(-1) of ST (groups B and F), 100 mg kg(-1) of free resveratrol (groups C and G) and inclusion complex of resveratrol (nanoparticles containing resveratrol) (groups D and H), and lastly an co-administration of both drugs (groups I and J). Behavioral tests (memory, anxiety and locomotion) were performed after treatment. Liver and brain fragments were collected to evaluate pathological changes, brain cysts counts, as well as oxidant and antioxidant levels. A reduction on the number of cysts in the brain of animals treated with both drugs combined was observed; there was also reduced number of lesions on both organs. This drug combined effect was also able to reduce oxidative and increase antioxidant levels in infected mice, which might be interpreted as a resveratrol protective effect. In addition, the combination of ST and resveratrol was able to prevent behavioral changes in infected mice. Therefore, the use of co-administration drugs enhances the therapeutic effect acting on a synergic way, reducing the oxidizing effects of the chemical treatment for toxoplasmosis. In addition, resveratrol in inclusion complex when co-administered with ST showed an improved therapeutic effect of ST reducing oxidative damage, liver damage and the number of cysts in the brain of T. gondii infected mice.
本研究旨在探讨白藜芦醇与磺胺甲恶唑 - 甲氧苄啶（ST）在疾病慢性期对实验性感染刚地弓形虫的小鼠进行治疗时的协同作用，研究内容涉及感染、行为以及氧化/抗氧化剂谱方面。在该研究中，60只小鼠最初被分为两组：未感染组（n = 24）和刚地弓形虫感染组（n = 36）。这两组随后又被细分为其他组，并分别用白藜芦醇（游离型和含白藜芦醇的包合物）单独处理以及与ST联合给药：A至D组由健康小鼠组成，E至J组由刚地弓形虫（VEG株）感染的动物组成。感染后20天开始治疗，连续10天口服剂量为0.5 mg kg⁻¹的ST（B组和F组）、100 mg kg⁻¹的游离白藜芦醇（C组和G组）以及白藜芦醇包合物（含白藜芦醇的纳米颗粒）（D组和H组），最后是两种药物联合给药（I组和J组）。治疗后进行行为测试（记忆、焦虑和运动能力）。收集肝脏和脑碎片以评估病理变化、脑囊肿计数以及氧化剂和抗氧化剂水平。观察到联合使用两种药物治疗的动物脑中囊肿数量减少；两个器官的病变数量也减少。这种药物联合作用还能够降低感染小鼠的氧化水平并提高抗氧化剂水平，这可能被解释为白藜芦醇的保护作用。此外，ST与白藜芦醇联合使用能够预防感染小鼠的行为变化。因此，联合使用药物以协同方式增强治疗效果，减少弓形虫病化学治疗的氧化作用。此外，白藜芦醇包合物与ST联合使用时显示出ST治疗效果的改善，可减少刚地弓形虫感染小鼠的氧化损伤、肝脏损伤以及脑中囊肿数量。
