Resveratrol livre e em complexo de inclusão associado ao sulfametoxazol-trimetropim em camundongos infectados experimentalmente com Toxoplasma gondii

Abstract

The Toxoplasma gondii is a protozoan of great clinical importance can cause functional and biochemical changes in the host cells mainly in the central nervous system. These changes are usually associated with the inflammatory response to tissue damage and cell oxidation in immunocompetent hosts. T. gondii infection stimulate the production of high levels of cytokines such as IL-12 and IFN-γ by cells of the immune system, consisting of a main point in parasite control and disease resistance. As a potent antioxidant, resveratrol has become an important research subject due to its antioxidant and anti-inflammatory properties. However, the mechanism by which resveratrol exerts its effects are hampered by the low solubility and bioavailability. Accordingly, one way to improve the bioavailability of resveratrol is to associate with inclusion complexes. Thus, this study aimed to investigate the benefits of resveratrol associated with sulfamethoxazole-trimethoprim (ST) in the treatment of experimentally infected mice with T. gondii. For the study, 60 mice were divided into two groups: non-infected (n = 24) and infected with T. gondii (n = 36). The two groups were divided into subgroups and treated with resveratrol (free and inclusion complex 2-hydroxypropyl-β-cyclodextrin) isolated and associated with ST. The groups A to D composed by healthy mice and groups E to J consisting of animals infected by T. gondii (VEG strain). The treatment started 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 (inclusion complex containing resveratrol) (groups D and H), as well as with an association of both drugs (groups I and J). Groups A and E were used as control, untreated. Behavioral tests (memory, anxiety and locomotion) were performed after treatment. Blood samples, liver and brain fragments were collected to evaluate the cytokine profile, pathological changes, brain cysts counts, as well as oxidant/antioxidant profile. Infected animals showed behavioral changes such as anxiety and memory loss. The combination ST and resveratrol was able to restore time latência in passive avoidance task. A reduction of the number of brain cyst was observed on animals treated with the combination of drugs. Infected animals show an increase in pro-inflammatory cytokines and reduction of anti-inflammatory cytokine (IL-10), as well as increased protein oxidation in liver and brain tissue. The combination of resveratrol and ST with free inclusion complex in increased the total antioxidant capacity (TAC) and ferric reducing antioxidant power (FRAP) levels in liver and brain that can be interpreted by the protective effect of resveratrol. In addition, resveratrol in inclusion complex form when combined with ST improved therapeutic effect of ST reducing oxidative damage in liver and brain, reducing the number of cysts in the treatment of mice infected with T. gondii. Therefore, it is possible to suggest that the ST with resveratrol on treatment of infected mice can exerts a protective effect on host cells. The resveratrol in inclusion complex form was the best treatment option, for controlled tissue and serum immune responses, as well as oxidative stress in mice infected with T. gondii.