RESUMO
Parkinson's disease (PD) is identified by the loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), and is correlated to aggregates of proteins such as α-synuclein, Lewy's bodies. Although the PD etiology remains poorly understood, evidence suggests a main role of oxidative stress on this process. Lippia grata Schauer, known as "alecrim-do-mato", "alecrim-de-vaqueiro", "alecrim-da-chapada", is a native bush from tropical areas mainly distributed throughout the Central and South America. This plant species is commonly used in traditional medicine for relief of pain and inflammation conditions, and that has proven antioxidant effects. We evaluated the effects of essential oil of the L. grata after its complexed with ß-cyclodextrin (LIP) on PD animal model induced by reserpine (RES). Behavioral assessments were performed across the treatment. Upon completion the treatment, the animals were euthanized, afterwards their brains were isolated and processed for immunohistochemical and oxidative stress analysis. The LIP treatment delayed the onset of the behavior of catalepsy, decreased the number of oral movements and prevented the memory impairment on the novel object recognition task. In addition, the treatment with LIP protected against dopaminergic depletion in the SNpc and dorsal striatum (STRd), and decreased the α-syn immunoreactivity in the SNpc and hippocampus (HIP). Moreover, there was reduction of the oxidative stability index. These findings demonstrated that the LIP treatment has neuroprotective effect in a progressive parkinsonism model, suggesting that LIP could be an important source for novel treatment approaches in PD.
Assuntos
Lippia , Fármacos Neuroprotetores , Óleos Voláteis , Doença de Parkinson , Transtornos Parkinsonianos , beta-Ciclodextrinas , Animais , alfa-Sinucleína/metabolismo , Lippia/metabolismo , Reserpina , Óleos Voláteis/efeitos adversos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Antioxidantes/metabolismo , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/metabolismo , Doença de Parkinson/metabolismo , Neurônios Dopaminérgicos/metabolismo , Modelos Animais de Doenças , beta-Ciclodextrinas/efeitos adversos , Substância Negra/metabolismoRESUMO
Recently, there have been numerous cases of leishmaniasis reported in different Brazilian states. The use of furazolidone (FZD) to treat leishmaniasis has been previously described; however, the drug is associated with adverse effects such as anorexia, weight loss, incoordination, and fatigue in dogs. Thus, in the present study, we prepared and evaluated inclusion complexes between FZD and ß-cyclodextrin (ß-CD) to guarantee increased drug solubility and reduce the toxicity associated with high doses. The FZD:ß-CD complexes were prepared by two different techniques (kneading and lyophilization) prior to incorporation in an oral pharmaceutical dosage form. Formation of the complexes was confirmed using appropriate physicochemical methods. Antileishmanial activity against L. amazonensis was tested in vitro via a microplate assay using resazurin dye and cytotoxicity was determined using the fibroblast L929 lineage. Solubility studies showed the formation of complexes with complexation efficiencies lower than 100%. Physicochemical analysis revealed that FZD was inserted into the ß-CD cavity after complexation by both methods. Biological in vitro evaluations demonstrated that free FZD and the FZD:ß-CD complexes presented significant leishmanicidal activity against L. amazonensis with IC50 values of 6.16⯵g/mL and 1.83⯵g/mL for the complexes prepared by kneading and lyophilization, respectively. The data showed that these complexes reduced the survival of promastigotes and presented no toxicity for tested cells. Our results indicate that the new compounds could be a cost-effective alternative for use in the pharmacotherapy of leishmaniasis in dogs infected with L. amazonensis.
Assuntos
Antiprotozoários/farmacologia , Furazolidona/farmacologia , Leishmania mexicana/efeitos dos fármacos , beta-Ciclodextrinas/farmacologia , Animais , Antiprotozoários/efeitos adversos , Brasil , Furazolidona/efeitos adversos , Testes de Sensibilidade Parasitária , Resultado do Tratamento , beta-Ciclodextrinas/efeitos adversosRESUMO
OBJECTIVES: Modified drug delivery systems have been developed to improve pharmacological properties of local anaesthetics. However, the inflammatory potential of these formulations was not investigated. This study compared the in-vitro effects of ropivacaine (ropi) in plain, liposomal (MLV) or 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) formulations on cell viability, apoptosis and cytokine (IL-1α, TNF-α, IL-6 and IL-10) release. METHODS: Human immortalized keratinocytes (HaCaT) and human immortalized gingival fibroblasts (HGF) were exposed to 1-100 µm ropi concentrations. The cell viability was measured by XTT and LIVE/DEAD assay. Apoptosis was performed by flow cytometry, and cytokine release was measured by ELISA assay. KEY FINDINGS: Human immortalized keratinocyte viability was reduced by ropi and both drug delivery systems. However, none of the formulations induced apoptosis. Results showed a differential regulation of IL-1α TNF-α, IL-6 and IL-10 by HaCaT and HGF. Ropi-HP-ß-CD increased twofold the IL-6 release by HGF in comparison with the control, while 100 µm ropi-MLV led to an increased release of all pro-inflammatory cytokines by HGF. CONCLUSION: The loss in cell viability was not related to cellular apoptosis. Ropi complexed with HP-ß-CD showed a similar cytokine release pattern when compared to the plain formulation. Thus, the HP-ß-CD form was a better drug carrier than the MLV form for ropivacaine drug delivery.
Assuntos
Amidas/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Sistemas de Liberação de Medicamentos/efeitos adversos , Fibroblastos/metabolismo , Queratinócitos/metabolismo , 2-Hidroxipropil-beta-Ciclodextrina , Apoptose/efeitos dos fármacos , Células Cultivadas , Humanos , Interleucina-10/metabolismo , Interleucina-1alfa/metabolismo , Interleucina-6/metabolismo , Lipossomos/efeitos adversos , Ropivacaina , Fator de Necrose Tumoral alfa/metabolismo , beta-Ciclodextrinas/efeitos adversosRESUMO
The preemptive analgesic efficacy and adverse effects of preoperatively administered piroxicam-β-cyclodextrin for post-endoscopic sinus surgery pain was determined in a prospective, double-blind, randomized, clinical study. Seventy-five American Society of Anesthesiologists status I-II patients, aged 18-65 years, were divided into three groups with similar demographic characteristics: group 1 received 20 mg piroxicam-β-cyclodextrin, group 2 received 40 mg piroxicam-β-cyclodextrin and group 3 received placebo orally before induction of general anesthesia. A blinded observer recorded the incidence and severity of pain at admission to the post-anesthesia care unit (PACU), at 15, 30, and 45 min in the PACU, and 1, 2, 4, 6, and 24 h postoperatively. All patients received patient-controlled morphine analgesia during the postoperative period and consumption was recorded for 24 h. During the PACU period, mean visual analogue scale values were significantly lower in groups 1 and 2 compared to group 3 (P < 0.05). During the postoperative period, morphine consumption was 3.03 ± 2.54, 2.7 ± 2.8, and 5.56 ± 3.12 mg for each group, respectively (P < 0.05). As a side effect, bleeding was observed in groups 1 and 3, nausea and vomiting in all groups, and edema only in group 3. However, no significant differences were detected in any of the parameters analyzed, which also included epigastric pain, constipation/diarrhea and headache. Similar hematological test results were obtained for all groups. Preemptive administration of piroxicam-β-cyclodextrin effectively reduced analgesic consumption, and 40 mg of the drug was more effective than 20 mg piroxicam-β-cyclodextrin without side effects during the postoperative period.
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Anti-Inflamatórios não Esteroides/administração & dosagem , Endoscopia/métodos , Dor Pós-Operatória/prevenção & controle , Piroxicam/administração & dosagem , Sinusite/cirurgia , beta-Ciclodextrinas/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Medição da Dor , Cuidados Pré-Operatórios , Estudos Prospectivos , Piroxicam/efeitos adversos , Adulto Jovem , beta-Ciclodextrinas/efeitos adversosRESUMO
The preemptive analgesic efficacy and adverse effects of preoperatively administered piroxicam-beta-cyclodextrin for post-endoscopic sinus surgery pain was determined in a prospective, double-blind, randomized, clinical study. Seventy-five American Society of Anesthesiologists status I-II patients, aged 18-65 years, were divided into three groups with similar demographic characteristics: group 1 received 20 mg piroxicam-beta-cyclodextrin, group 2 received 40 mg piroxicam-beta-cyclodextrin and group 3 received placebo orally before induction of general anesthesia. A blinded observer recorded the incidence and severity of pain at admission to the post-anesthesia care unit (PACU), at 15, 30, and 45 min in the PACU, and 1, 2, 4, 6, and 24 h postoperatively. All patients received patient-controlled morphine analgesia during the postoperative period and consumption was recorded for 24 h. During the PACU period, mean visual analogue scale values were significantly lower in groups 1 and 2 compared to group 3 (P < 0.05). During the postoperative period, morphine consumption was 3.03 +/- 2.54, 2.7 +/- 2.8, and 5.56 +/- 3.12 mg for each group, respectively (P < 0.05). As a side effect, bleeding was observed in groups 1 and 3, nausea and vomiting in all groups, and edema only in group 3. However, no significant differences were detected in any of the parameters analyzed, which also included epigastric pain, constipation/diarrhea and headache. Similar hematological test results were obtained for all groups. Preemptive administration of piroxicam-beta-cyclodextrin effectively reduced analgesic consumption, and 40 mg of the drug was more effective than 20 mg piroxicam-beta-cyclodextrin without side effects during the postoperative period.