Programa de Pós-Graduação em Ciências Farmacêuticas
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Doctoral Thesis Propriedades antioxidantes da coenzima Q10 e do zinco no estado nutricional de indivíduos com Síndrome de Down(Universidade Federal do Rio Grande do Norte, 2022-05-12) Silva, Saulo Victor e; Thornton, Maria das Graças Almeida; https://orcid.org/0000-0002-5587-0922; http://lattes.cnpq.br/0321740024191482; https://orcid.org/0000-0003-0793-2647; http://lattes.cnpq.br/8278651522984535; Souza, Karla Simone Costa de; https://orcid.org/0000-0002-8541-1444; http://lattes.cnpq.br/2262063068881600; Silva, Marcelo de Sousa da; Neves, Juliana Padilha Ramos; Silva, Gabriel Araújo daDown Syndrome (DS) is known for the trisomy of chromosome 21, characterized by several physiological and metabolic alterations, among them the presence of oxidative stress as a result of the imbalance between the amount of reactive oxygen species (ROS) and antioxidant enzymes. Compounds with antioxidant properties such as coenzyme Q10 (CoQ10) and zinc (Zn) may reduce the cellular imbalances caused by the increase of ROS. Thus, the present study aimed to evaluate the antioxidant potential of CoQ10 combined with Zn in vitro and in individuals with DS. Initially, an in vitro study was performed to evaluate the antioxidant potential of CoQ10, Zn, and the combination between them in a model of oxidative stress in CHO-K1 cells induced by Arsenic (As). The determination of cell viability for each treatment was done by crystal violet, MTT and Alamar Blue® colorimetric assays. The antioxidant activity was evaluated by DPPH radical reduction assays, ferric reducing power (FRAP), aqueous hydroperoxide formation and ROS determination. In parallel, a clinical, double-blind, randomized study was conducted in children with DS aged 2 to 9 years to evaluate the effect of supplementation of CoQ10 at 4 mg/kg/day, Zn at 11 mg/day and CoQ10+Zn (CoQ10 at 4 mg/kg/day and Zn at 11 mg/day). Biochemical parameters such as glycemic control, lipid profile and renal function, food consumption, anthropometric parameters, lipid peroxidation, antioxidant potential by superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic activity, and non-enzymatic by glutathione reductase (GSH), and serum Zn profile were evaluated. In the in vitro study, cell viability assays showed that both CoQ10 and its combination with Zn showed cytoprotective effect independent of the concentrations analyzed, unlike cells treated only with Zn when exposed to cell stress situations. CoQ10 showed antioxidant activity, independent of the concentration used, but when combined with Zn it did not show any increase in its activity at the cellular level. However, Zn in high concentrations showed a pro-oxidant effect, causing cellular damage. In the clinical study, the individuals presented a serum Zn concentration below the recommended levels, thus, Zn supplementation in combination with CoQ10 could add nutritional value to the antioxidant activity of CoQ10, presenting satisfactory results to the supplementation of these micronutrients. Thus, the in vitro study observed a greater Zn deficiency in children with DS and that the supplementation with CoQ10, when combined with Zn, differently from what was observed in the in vitro study, demonstrated that the supplementation with CoQ10, Zn, and the combination CoQ10+Zn enables an increase in antioxidant activity, besides reducing lipid peroxidation and ensuring the preservation of antioxidant enzymes. Regarding the in vivo study, a higher Zn deficiency was observed in children with DS and supplementation with CoQ10 when combined with Zn. Thus, the study concluded that it may present an increase in antioxidant activity, adding nutritional value to the antioxidant potential of CoQ10, besides reducing lipid peroxidation and ensuring the preservation of antioxidant enzymes.Master Thesis Atividade anti-inflamatória e antinociceptiva dos extratos brutos e frações de Eugenia uniflora e Libidibia ferrea in vivo(2017-06-29) Falcão, Tamires Rocha; Araújo, Aurigena Antunes de; Guerra, Gerlane Coelho Bernardo; http://lattes.cnpq.br/5677318431530876; http://lattes.cnpq.br/3531154240424211; http://lattes.cnpq.br/9703962688376811; Pedrosa, Matheus de Freitas Fernandes; http://lattes.cnpq.br/2929963416385218; Batista, Leônia Maria; http://lattes.cnpq.br/0601720493634706The species Libidibia ferrea belongs to the family Fabaceae, popularly known as pau-ferro or jucá, being used in traditional medicine as antibacterial, antiulcerogenic, anti-inflammatory and analgesic. Eugenia uniflora belongs to Myrtaceae family, being known as pitanga, popularly used in the treatment of diarrhea, inflammation, hyperglycemia and hypertension. An analysis of medicinal plants as a source of new drugs for the treatment of several diseases, and involvement of the inflammatory process in numerous diseases, and strong indications of pharmacological activity associated with the presence of bioactive substances present in these species, With the aim of evaluating an anti-inflammatory and antimociceptive activity of the crude extracts and phrases of Libidíbia ferreira and Eugenia uniflora, through the model of carrageenan-induced peritonitis, hot plate test and abdominal contortions induced by acetic acid in Swiss mice Species Mus musculus. From crude and crushed vegetable materials, crude extracts and Eugenia uniflora fractions (crude aqueous extract, aqueous fraction, hexane fraction and ethyl acetate fraction) and Libidibia ferrea (crude aqueous extract, extracts Crude extracted with ethanol 20, 40, 60 and 80%, fraction ethyl acetate and aqueous fraction). The chromatographic analyzes of the extracts and the fractions allowed to separate and identify the gallic acid hydrolysable tannins, with retention time of approximately 8.7 minutes, and ellagic acid, with retention time of 25.1 minutes, also detected the flavonoid myricitrin, Confirmed With the chromatographic data of the standards. In the evaluation of leukocyte migration, the crude extract fractions of Eugenia uniflora and Libidibia ferrea at doses of 50 mg / kg, 100 and 200 mg / kg reduced the number of inflammatory cells to the site of inflammation (p <0.001), comparing the treated groups With the positive control group. The decrease in the cellular influx was accompanied by a decreased marking of myeloperoxidase activity, reduction of MDA, and showed protection against glutathione depletion (p <0.001). The administration of the crude extracts and fractions produced a peripheral antinociceptive response in all the doses tested, reducing the number of product contours by means of an acoustic in mice, but demonstrating little central analgesic activity, being evaluated by the hot plate test. The results indicate that these plants are anti-inflammatory and antinociceptive activities. However, other studies are indispensable for the elucidation of its pharmacological properties, studies of inscription analysis and toxic properties.Master Thesis Associação entre estresse oxidativo e a osteopenia diabética: efeito da suplementação com cálcio, fósforo e vitamina E(2003-08-29) Rodrigues, Alanna de Sousa; Thornton, Maria das Graças Almeida; Rezende, Adriana Augusto de; ; http://lattes.cnpq.br/4245215108740331; ; ; http://lattes.cnpq.br/0819752921364531; Brandão Neto, José; ; http://lattes.cnpq.br/6905360146925949; Queiroz, Maria Goretti Rodrigues de; ; http://lattes.cnpq.br/8792842617230865The increase of EROs concentration, through diabetes mellitus, can alter the normal bone metabolism, causing osteopenia. A calcium, fosforum and vitamin E supplementation, can be a very good action in bone. In thi study were used male Wistar rats (n=125), weight ranging from 250 – 350g, and were divided in three groups: group 1 control (n=45) group 2 experimental diabetic (n=45) and group 3 supplementadies diabetic (n=35) in calcium, fosforum and vitamin E. The animals were inuced with streptozotocin (45mg/Kg ) and killed in periods of 1 to 5 days after the indution e 5, 30, 60 and 90 days after installation of experimental diabetes mellitus. Animals with glycemia ≤ 250 mg/ dL was considered diabetics.In each period was realized determinations of Thiobarbituric Acid Reactive Substances and levels of reduced glutathione in blood and brain, histomorfometric measurement of left fermurs, and dosages of alkaline phosphatase, acid phosphatase, ionizable calcium, total calcium, phosphorus, magnesium, glycemia, creatinin and albumin in serum and glucose, phosphorus, magnesium, creatinine and clearence of creatinin in urine. Thiobarbituric Acid Reactive Substances at brain and plasma, choose higher at group 2 in relation group 1, and reduced in group 3, in period of 90 days. The levels of reduced glutathione in brain and blood, at 90 days, was decreased in group 2 and increased at group 3. The histomorphometric results show a less in middle of 50% in trabecular bone volume analysed per distance between the trabeculaes thickness of trabeculae and bone quantity in experimental diabetic animals in comparison to the control group and for controls group and, supplemented animals this lose reduced very much arriving sizes near found in control group. The activity of alkaline phosphatase showed superior values in relation of groups 2 and 3, about comparing group 1 and acid phosphatase increased higher in groups 2 and 3, about all controls, in a 90 days. The serum concentration of phosphorus, magnesium, ionazle calcium, total calcium and creatinine, didn´t show alterations, and the results are well if compare the reference result. The albumin serum showed less to group 2 and 3. The urine analyse showed significative glycosúria to groups 2 and 3 if compared with group 1. In relation phosphatury, observed a significative increase principally to group 3 and creatinine clearance relation wasn´t observed differences to group 2 and 3. The results observed suggest that calcium, phosphorus and vitamin E supplementation, decreased the oxidative alterations which the diabetics were the cause, and helped bone metabolism, decreasing the lose bone that ocurr in this syndromeMaster Thesis Influência do tratamento com ácido lipoico sobre o metabolismo ósseo e perfil antioxidante de mulheres na perimenopausa(Universidade Federal do Rio Grande do Norte, 2010-02-22) Freire Neto, Francisco Paulo; Rezende, Adriana Augusto de; Almeida, Maria das Graças; ; http://lattes.cnpq.br/0321740024191482; ; http://lattes.cnpq.br/4245215108740331; ; http://lattes.cnpq.br/8004536021600117; Azevedo, George Dantas de; ; http://lattes.cnpq.br/1088076378928302; Hirata, Rosário Dominguez Crespo; ; http://lattes.cnpq.br/9991478856647926Bone is a dynamic tissue that is in constant process of remodeling in response to mechanical stress and hormonal changes. This study aimed to understand the relationship between the biochemical changes, which women in the menopausal transition are subject to, and how the use of an alternative therapy with lipoic acid (LA) could influence these changes. The study of double-blind, was carried out in perimenopausal women that underwent a three month treatment with 600 mg of AL compared with another group that received placebo during the same period. This study showed that women had a waist circunference and body mass index above the values recommended by WHO (WC ≥ 80 cm; BMI > 25kg/m2). Associated with this, these women had increased concentrations of total cholesterol and triglycerides, and borderline LDL (Total Cholesterol > 200mg/dL; Triglycerides > 150mg/dL; LDL >130mg/dL). These changes were not affected by treatment with AL. There were no shifts in liver profile (ALT, AST and GGT), kidney profile (urea, creatinine, total protein and albumin), mineral profile (Total Calcium, Ionized Calcium, Phosphorus and Magnesium) as well in bone markers (osteocalcin, Total Alkaline Phosphatase and Tartrate Resistant Acid Phosphatase) after treatment with LA. The results of the oxidative profile showed that treatment with LA decreased GPx activity (p < 0,01), while for the TBARS, GSH and SOD activity there were no differences. With regard to SOD, this enzyme will submit to be high in the placebo group after 3 months of study (p<0,05). The expression of RANKL mRNA was reduced (p < 0,05) and of RANK increased (p <0.001), after treatment with LA, while the expression of IL-6 and TNF-ɑ genes were no changed. We conclude that women already in the perimenopause stage have changes in lipid profile and body composition that could induce shifts in oxidative and bone metabolism. However, LA treatment has provided an effective effect in the oxidative and bone profile since the earliest markers such as GPx activity and mRNA expression of RANKL, respectively, were reduced associated with no change in SOD activity. These results suggest a beneficial and protective effect of LA, indicating it potential as an alternative treatment to help the to prevent the complications associated with estrogen deficiencyMaster Thesis Avaliação dos parâmetros de estresse oxidativo no lúpus eritematoso(Universidade Federal do Rio Grande do Norte, 2009-03-27) Costa, Tatiana Xavier da; Lemos, Telma Maria Araujo Moura; ; http://lattes.cnpq.br/4311626091295357; ; http://lattes.cnpq.br/1775286763156268; Vilar, Maria José Pereira; ; http://lattes.cnpq.br/4265369922470937; Cavagis, Alexandre Donizeti Martins; ; http://lattes.cnpq.br/0907530041669620OBJECTIVE: The aim of this work was to analyse some oxidative stress parameters in patients of Systemic Lúpus Erythematosus. PATIENTS AND METHODS: Determinations of reduced glutathione content in whole blood were carried out. The activity of superoxide dismutase, gluthatione peroxidase and catalase in erythrocytes and the concentration of reactive substances of acid thiobarbituric in plasma of patients female (n =19) with SLE no activity of disease (Mex-SLEDAI < 2), with average ages of 32 ± 11 years, through the spectrophotometrical methods and from healthy individuals (n =30). Statistical data were analyzed by student t-test, p<0,05. RESULTS: Our data indicated a significant decrease on the activity of catalase and significant increase on the concentration of reactive substances of acid thiobarbituric in patients with SLE comparing with healthy individuals. There was no significant difference in other parameters. CONCLUSION: The results showed that oxidative stress has a role in the pathogenesis of the disease in SLE, even in patients without active disease.Master Thesis Alterações nas concentrações das SRAT, conteúdo de GSH e atividade da CAT em pacientes com esquistossomose aguda(Universidade Federal do Rio Grande do Norte, 2008-01-30) Cunha, Gina Michelle Macêdo da; Freire, Ana Cláudia Galvão; ; http://lattes.cnpq.br/3215086103105355; ; http://lattes.cnpq.br/9927438721492551; Almeida, Maria das Graças; ; http://lattes.cnpq.br/0321740024191482Schistosomiasis is an ancient disease caused by helminth Schistosoma mansoni and is a public health problem in Brazil. The granulomatous lesion, typical of the disease, associates itself with increase in the oxidative damage through the generation of free radicals. The aim of this work was to evaluate the occurrence of changes in parameters oxidant / antioxidant that are part of the human defense system, and observe whether they would cause oxidative stress in subjects with schistosomiasis. Moreover, correlating with some biochemical and hematological parameters. Two groups were selected for study, consisting of individuals of both sexes, aged between 16 and 30 years. A control group, formed by individuals without schistosomiasis (n = 30) and a test group, formed by individuals with schistosomiasis (n = 30). The evaluation of lipid peroxidation in plasma was performed by determination of malondialdehyde and antioxidant defense by the quantification of reduced glutathione and catalase activity. For the parameters that assess oxidative stress, the results showed a decrease in the content of reduced glutathione and no change in the activity of catalase, with an increase in the value of malondialdehyde. Therefore, the data found suggest the occurrence of oxidative stress in subjects with schistosomiasis. Of the parameters that assess hepatic function, only levels of aspartate aminotransferase have been high, while there was a decrease of bilirubine. There was a significant change in the lipid profile (p <0.5), however with regard to the renal function of patients, there was a decrease in creatinine. The assessment hematological, made through hemogram and the quantification of hemoglobin, shows increase of eosinophils individuals in the group test, which can be related to the presence of the parasite. The amendments suggest the involvement of oxidative stress in the pathophysiology of this disease