Navegando por Assunto "Dapsona"
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Item Acesso aberto (Open Access) Alterações oxidativas e inflamatórias induzidas pela dapsona no sangue e no córtex pré-frontal de camundongos: efeitos do ácido alfa-lipóico(Universidade Federal do Pará, 2018-12-14) GOMES, Bruno Alexandre Quadros; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390Dapsone (DDS), a drug used in leprosy multidrug therapy, can cause many adverse reactions and intoxications, inducing the generation of reactive oxygen species (ROS) and imbalance in the redox state, increase methemoglobin (MetHb) formation, hemolysis and release of heme and iron free, which may interfere with redox homeostasis in more vulnerable regions, such as prefrontal cortex (PFC), causing neurotoxicity and even neuroinflammation. In this sense, antioxidant compounds with chelating properties such as α-lipoic acid (ALA) may play a key role in combating or preventing these alterations. Thus, this work aims to evaluate the effect of DDS on MetHb formation, peripheral oxidative stress, and oxidative changes and neuroinflammation in PFC, as well as, effects of ALA. For this, was induced MetHb formation in Swiss mice with DDS 40mg/kg ip for 5 days. Two hours after DDS administration, ALA was given at two concentrations (12.5 and 25 mg/kg). Besides MetHb percentage, total equivalent antioxidant capacity (TEAC), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) thiobarbituric acid reactive substances (TBARS), and iron concentrations in blood and PFC were evaluated, as well as, IL-1β, IL-17, and IL-4 cytokine concentrations, and de F4/80+, GFAP, and BDNF expression in PFC. Our results show that DDS induces the MetHb formation in red blood cells of mice, however, ALA was able to prevent or reverse the oxidation of hemoglobin induced by DDS at two used concentrationns. DDS reduced antioxidant capacity (TEAC) in plasma and red blood cells; decreased erythrocyte GSH, CAT, and SOD; and increased TBARS and plasma iron; however, ALA at two concentrations increased or reestablished TEAC in plasma and red blood cells at baseline levels. In addition to increasing or reestablishing GSH levels, SOD, and CAT in red blood cells, and decreased TBARS and iron levels, mainly in euthanized animals 4h after treatment. Curiously ALA 50mg/kg increased plasma iron concentrations. The treatment with DDS 40mg/kg also reduced TEAC, GSH, SOD e CAT in the PFC of the mice and increased TBARS and iron, characterizing oxidative stress, mainly in euthanized animals in 24h after treatment. Treatment with ALA increased or restored TEAC and GSH; and increased SOD and CAT in 12,5mg/kg concentration in euthanized animals 4h after treatment, as well as reducing TBARS levels and decreasing or preventing iron overload, mainly in euthanized animals 24h after treatment. DDS also promoting microglial and astrocyte activation in PFC, through F4/80+ e GFAP expression., with increased IL-1β and IL-4 production, and BDNF reduction, on the other hand, ALA 25mg/kg reduced GFAP and IL-1β expression, besides increased BDNF, suggesting that DDS also can cause neuroinflammation, and ALA presents antioxidant and anti-inflammatory properties against toxicity caused by DDS. These results suggest that ALA is promising and plays an important role in the prevention and/or formation of MetHb, reestablishment of redox balance and iron concentrations in both blood and PFC. Thus, ALA may be a usefull adjuvant therapy in DDS-induced toxicity, with lower toxicity and increasing adherence to treatment of leprosy patients.Item Acesso aberto (Open Access) Avaliação antropométrica e a concentração plasmática de dapsona em pacientes com hanseníase na cidade de Belém-Pará(Universidade Federal do Pará, 2011-08-31) MOURA, Fernanda Maria Lima; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098Hanseniasis is a serious problem of public health in the state of Pará, with high incidence and prevalence rates. This paper aimed to evaluate the nutritional status of patients bearing multibacillary hanseniasis relating them to their plasma concentration of dapsone. It is a transversal epidemiological study performed with 29 individuals of both sexes with multibacillary hanseniasis referred to the Ambulatório do Núcleo de Medicina Tropical da Universidade Federal do Pará. Social-demographic, anthropometric, plasma concentration of dapsone and use of prednisone indicators were evaluated. It was evaluated the nutritional status through the body mass índex and percentage of body fat. Plasma determination of dapsone was performed through high efficiency liquid chromatography. Other data were obtained through a semi-structured interview form which was answered by the patients. The results have pointed out that most patients were male, average age of 41.73 (±13.14) and living in the municipality of Belém (58.6%).They have lived into an unfavorable social situation, minimum wage family income (65.6%) and low schooling to the elementary level (51.7%). The nutritional status, according to the body mass index has indicated that 48.3% of the patients were eutrophic. However, 51.6% presented overweight and 13.8% out of them were obese. As for the percentage of body fat, 48.3% were obese. It was observed that 37.9% of the patients have already presented a hansenic reaction, with predominance of type 1 reaction (RR) and 34.5% used prednisone. From the patients using prednisone, 60.0% were overweight and 50.0% were obese, according to the body mass index and percentage of body fat, respectively, though without any statistical significance (p>0.05), when compared to the ones who did not. The plasma average concentration of dapsone in the patient was 0.56 μg/mL. As for the body mass index, it was verified that as the weight of the patient raised, the plasma concentration of dapsone reduced. Eutrophic, pre-obese and obese patients presented plasma concentrations of 0.56 μg/mL, 0.54 μg/mL and 0.44 μg/mL, respectively. Considering the percentage of body fat, it was observed that the average plasma concentration of dapsone was 0.54 μg/mL in eutrophic and obese patients. It was not evidenced any statistical significance between the plasma concentration of dapsone and the nutritional status (p>0.05). Conclusion: The nutritional status did not interfere in the plasma concentration of dapsone, independently from the nutritional parameter, body mass index or percentage of body fat used as well as the use of prednisone was not related to the gain of weight.Item Acesso aberto (Open Access) Clinical applications and methemoglobinemia induced by dapsone(2014-10) OLIVEIRA, Fábio Rodrigues de; PESSÔA, Mariely Cristine Amador; ALBUQUERQUE, Rosyana de Fatima Vieira de; SCHALCHER, Taysa Ribeiro; MONTEIRO, Marta ChagasDapsone is a synthetic sulfone that is used as an antibiotic in humans and animals to prevent and treat diseases including leprosy, tuberculosis, malaria, and Pneumocystis carinii pneumonia and Toxoplasma gondii encephalitis in acquired immune deficiency syndrome (AIDS) patients as well as in anti-inflammatory conditions, such as dermatitis herpetiformis. However, this drug is also associated with several adverse effects, including dose-related hemolysis, methemoglobinemia, psychosis, peripheral neuropathy, agranulocytosis, aplastic anemia, hypersensitivity syndrome, sulfone syndrome, and others. Of these effects, methemoglobinemia is the most common side effect of dapsone, which leads to functional anemia and cellular hypoxia with symptoms of cyanosis, headache, fatigue, tachycardia, weakness, and dizziness. Thus, this review summarizes relevant information on the structure, mechanism of action, clinical indication, and adverse reactions of dapsone.Item Acesso aberto (Open Access) Efeito da dapsona na geração de estresse oxidativo em pacientes com hanseníase em uso de poliquimioterapia(Universidade Federal do Pará, 2011) SCHALCHER, Taysa Ribeiro; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390Inflammation caused by Mycobacterium leprae infection and drugs with oxidative properties such as dapsone, are risk factors to induce the oxidative stress in leprosy patients. This study aims to determine plasma concentrations of dapsone in leprosy patients in use of multidrug therapy (MDT), correlating the development of oxidative stress. For the study, healthy individuals and leprosy patients were selected, followed before (D0) and after the third MDT-supervised dose (D3). The plasma concentrations of dapsone in patients under treatment (D3) were evaluated by high performance liquid chromatography. The oxidative stress was performed by methemoglobin (MetHb) and Heinz bodies determination, concentrations of reduced glutathione (GSH), nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TEAC) and enzymatic activity of catalase (CAT), superoxide dismutase (SOD) in blood. In the study were obtained 23 samples from leprosy patients in D0 and 13 in D3; and 20 healthy and without leprosy subjects. In patients before treatment (D0) were observed increase of NO (D0 = 18.91 ± 2.39, control = 6.86 ± 1.79mM) and significant reduction of the activity of SOD enzyme (D0 = 69.88 ± 12.26, control = 138.42 ± 14.99 nmol/mL). In MDT-treated patients (D3), the dapsone concentration in plasma was of 0,552 ± 0,037 μg / mL, and they showed Heinz bodies presence and significant increase in the MetHb percentage (D3 = 3.29 ± 0.74, control = 0051 ± 0.66%). In this patients also were observed increase of the GSH levels (D3=7.01 ± 1.9; control =3.33 ± 1.9 μg/mL) and decrease of the CAT activity (D3 = 10.29 ± 02.02, control = 19:52 2:48 ± U / g protein). However, MDA levels in D0 and D3 patients didn’t show changed, while TEAC levels, in this patients, significantly increased (D0 = 2.90 ± 0.42; D3 = 3.04 ± 0:52, control = 1.42 ± 0.18 μmol / mL). These data suggest that the MDT is mainly cause for oxidative stress, because it induced the generation of oxidative damage identified by Heinz bodies’ presence and increase in the MetHb percent.Item Acesso aberto (Open Access) O efeito in vitro dos compostos ácido alfa-lipoico e resveratrol em parâmetros do estresse oxidativo durante o uso da poliquimioterapia para hanseníase(Universidade Federal do Pará, 2014-10-20) PESSÔA, Mariely Cristine Amador; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390The leprosy is an infectious disease that represents a major preoccupation in global public health in 21st century. The treatment with Multi Drug Therapy (MDT) approved by the World Health Organization (WHO) is the best treatment to Mycobacterim leprae infection; however, is one of the factors of increasing Reactive Oxygen Species (ROS) production and the development of methemoglobinemia and hemolytic anemia in these patients. The aim of this study was to verify the oxidative damage in leprosy patients receiving MDT, by evaluation of hematological and oxidative stress biomarkers, and identify the effects of in vitro treatment with antioxidants alpha-lipoic acid (ALA) and resveratrol (RSV) in antioxidant enzymes activity and prevention of methemoglobinemia. The results revealed a decrease in RBC count and reticulocytosis in patients receiving MDT during the 4th and 7th month of treatment. The percentual of methemoglobin increased since the fifth month of treatment with MDT, and the treatment with 100 μM RSV-treated and ALA-treated preserved the values similar to control group only in 4th to 6th month of MDT samples. The leprosy patients presented values of SOD activity similar to the control group and a decreased CAT activity, leading to an inbalance in the ratio of both enzymes and possibly resulting in an over-producing of H2O2. The treatment with RSV and ALA in 100 μM and 500 μM concentrations increases twice the SOD activity in 4th month patient samples; however, these concentrations did not change CAT and SOD activities found in leprosy patients. Such results demonstrate that RSV and ALA did not show antioxidant activity in installed oxidative stress, and subsequent studies are necessary to evaluate dose-dependent and time-dependent concentrations of RSV and ALA to prevent oxidative damage in chronic infectious diseases.Item Acesso aberto (Open Access) Efeito protetor de antioxidantes na metemoglobina e no dano em dna induzidos pela dapsona-hidroxilamina in vitro(Universidade Federal do Pará, 2016-06-21) GOMES, Antonio Rafael Quadros; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390Dapsone (DDS) is one of the drugs used in polychemotherapy of leprosy associated with rifampicin and clofazimine. Of these drugs, DDS is primarily responsible for adverse reactions, such as methemoglobinemia and hemolytic anemia. These reactions are related to the DDS metabolite, dapsone hydroxylamine (DDS-NOH). In an attempt to promote the reduction of toxic effects are studied alternative therapies with antioxidants. This work aimed to evaluate the protective effect of N-acetylcysteine (NAC), A. brasiliensis and Glutathione ethyl ester (GSH-EE) in methemoglobin (MetHb) and DNA damage induced by DDS-NOH in vitro , correlating to oxidative stress parameters. For this, suspensions of human erythrocytes to 50% were pre- and post-treated with NAC, A. brasiliensis and GSH-EE in different concentrations, being exposed groups DDS-NOH to induce the formation MetHb. It also assessed whether the activity of enzymes-SOD and CAT and GSH levels, TEAC and MDA. In leukocytes evaluated the induction of ROS intracellularly using DCFH-DA and the damage to DNA by comet assay. The results showed that the DDS-NOH metabolite was capable of inducing MetHb in vitro, this dose-dependent effect. Regarding the pre-treatment, all the antioxidants prevented MetHb formation induced by DDS-NOH, as well as post-treatment. For SOD, only the pre-treatment with NAC and A. brasiliensis reduced SOD activity. In the post-treatment, there was increased when treated with antioxidants. Pre-treatment with NAC and GSH-EE increased CAT activity, moreover A. brasiliensis reduced, as after treatment with antioxidants. As for GSH levels, pre-treatment with NAC and GSH increased A. brasiliensis, on the other hand, did not alter after treatment. Regarding TEAC did not change. With respect to oxidative damage in the pre-treatment A. brasiliensis and GSH-EE reduced MDA. In the post-treatment, there was an increase in group A. brasiliensis and reduced GSH-EE group. Only the NAC was shown to be effective in removing the intracellular ROS induced by DDS-NOH in leukocytes. While in erythrocytes, a NAC and A. brasiliensis were able to reduce this effect. In the study of the comet assay, the DDS-NOH was able to induce DNA damage in peripheral blood leukocytes, however this damage was reduced when treated with NAC and A. brasiliensis. It can be concluded from our data that the evaluated antioxidants have therapeutic potential in the prevention of MetHb and DNA damage induced by DDS-NOH in vitro, more effective NAC against these effects.Item Acesso aberto (Open Access) Efeito protetor do ácido alfa lipóico sobre a lesão hepática, induzida por dapsona em modelo animal(Universidade Federal do Pará, 2018-07-06) SAKAI, Joni Tetsuo; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390The liver is the main organ involved in the biotransformation of xenobiotics, with the ability to convert hydrophobic compounds into water soluble, more easily eliminated by the body. Dapsone (DDS) is part of the multidrug therapy (MDT) of leprosy treatment, its metabolite is related to the generation of free radicals in hematological and neural cells, being thus directly involved in the main adverse reactions caused by its use. Due to its conversion cycle, which involves the reaction with iron present in the liver, DDS also accumulates in the liver, remaining longer in this organ, thus favoring tissue damage, such as drug hepatitis. In this context, the objective of the present study was to evaluate the protective effect of Alpha Lipoic Acid (ALA) on the liver damage caused by DDS in mice, after treatment. In this study, treatment with dapsone induced hepatic damage, with increase of Aspartate aminotransferase and alkaline phosphatase, as well as oxidative stress, by increasing lipid peroxidation and decreasing both glutathione levels and total antioxidants. These processes may be associated with accumulation of hepatic iron in the body. Already post-treatment with the antioxidant Alpha Lipoic Acid, this was able to decrease the levels of Aspartate aminotransferase and Alkaline Phosphatase, reverse lipid peroxidation and raise levels of GSH and total antioxidants. In addition, ALA also inhibited the accumulation of hepatic iron induced by dapsone in mice. Our results indicate that the antioxidant tested has a therapeutic potential against hepatic damage caused by dapsone in patients with leprosy.Item Acesso aberto (Open Access) Efeitos do quelante de ferro, a deferoxamina, sobre as alterações oxidativas e cognitivas induzidas pela dapsona, em modelo animal(Universidade Federal do Pará, 2020-11-17) MENDES, Paulo Fernando Santos; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/ 0000-0002-3328-5650Dapsone (DDS) is an antibiotic that works by inhibiting folate synthesis, showing good bacteriostatic action. However, it can lead to severe adverse events such as neurological disorders, methemoglobinemia and hemolysis. These hematological disorders lead to the alteration of iron homeostasis and thereby increase the formation of ROS that can lead to cellular and tissue damage. This change plays an important role in neurodegenerative diseases, whether as a causative and / or intensifying agent in these diseases. In this context, we used an iron chelator, deferoxamine (DFX), to evaluate its effects on the formation of ROS triggered by the increase in free iron induced by the use of DDS. For this, the alteration of iron homeostasis was induced in Swiss mice, using DDS, followed by the administration of DFX. After that, oxidative stress parameters were measured in the hippocampus and plasma, in addition to the measurement of iron levels. Our results showed that DDS decreased TEAC and that DFX treatment was restored. In addition, DDS decreased GSH and DFX treatment was restored. It increased the LPO and the treatment with DFX reduced this effect, increased the concentration of iron and that was reversed by the treatment with DFX. Additionally, the animals were submitted to the Morris water maze, where our results showed that animals treated with DDS showed a reduction in mnemonic capacity and that treatment with DFX was able to inhibit loss. These results suggest that the use of iron chelators may be an alternative to reduce the effects of iron accumulation on the nervous system observed in neurodegenerative diseases.Item Acesso aberto (Open Access) Methemoglobinemia and dapsone levels in patients with leprosy(2010-06) VIEIRA, José Luiz Fernandes; RIVERA, Juan Gonzalo Bardález; MARTINS, Ana de Nazaré Silva; SILVA, Jorge Pereira da; SALGADO, Claudio GuedesThe objective of this work was to determine the methemoglobinemia and correlate with dapsone levels in multibacillary leprosy patients under leprosy multi-drug therapy. Thirty patients with laboratory and clinical diagnosis of multibacillary leprosy were enrolled. Dapsone was analyzed by high performance liquid chromatography and methemoglobinemia by spectrophotometry. The mean dapsone concentrations in male was 1.42 g/mL and in female was 2.42 g/mL. The mean methemoglobin levels in male was 3.09 µg/mL; 191%, and in female was 2.84 ± 1.67%. No correlations were seen between dapsone levels and methemoglobin in male and female patients. Our results demonstrated that the dosage of dapsone in leprosy treatment does not promote a significant methemoglobinemia.