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1.
Biomedicines ; 11(9)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37760978

RESUMO

Hyperuricemia, the metabolic alteration that leads to gout or gouty arthritis, is increasing worldwide. Glycoconjugated triazole-phthalimides show potent anti-inflammatory activity. The aim of this study was to evaluate the anti-hyperuricemia effect of glycoconjugated triazole-phthalimides. To develop hyperuricemia, groups of mice received orally potassium oxonate (250 mg/kg) for 7 days, and F2, F3 and F4 glycoconjugated triazole-phthalimides (20 mg/kg), allopurinol (300 mg/kg), and 1% carboxymethylcellulose; indomethacin (2 and 4 mg/kg) was the positive control for anti-arthritic effect. Genotoxic and mutagenic effects were evaluated by the comet and micronucleus assays, respectively. The hemolytic action of the compounds was evaluated. Phthalimides F2, F3 and F4 significantly reduced the levels of serum uric acid, creatinine and urea in hyperuricemic animals. In addition, the compounds were efficient in reducing protein denaturation in a dose-dependent manner. In an interesting way, the histopathological analysis of kidneys from groups treated with F2, F3 and F4 showed a glomerular architecture, with the Bowman's capsule and renal tubules having a normal appearance and without inflammatory changes. Also, F2 and F4 showed a small increase in micronuclei, indicating a low mutagenic effect, whilst by comet assay only, we could infer that F4 affected the frequency and damage index, thus indicating a very small genotoxic action. Similarly, the phthalimides showed a low degree of erythrocyte hemolysis (<3%). Our data demonstrate that the new glycoconjugate triazole-phthalimides have potential to treat hyperuricemia and its secondary complications, such as gouty arthritis, with a low to non-significant rate of erythrocytes hemolysis, genotoxicity and mutagenicity making these molecules strong candidates as pharmaceutical agents for treatment requiring uric-acid-lowering therapy.

2.
Acta Trop ; 245: 106965, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37295486

RESUMO

The present work aimed to carry out in vitro biological assays of thiazole compounds against adult worms of Schistosoma mansoni, as well as the in silico determination of pharmacokinetic parameters to predict the oral bioavailability of these compounds. In addition to presenting moderate to low cytotoxicity against mammalian cells, thiazole compounds are not considered hemolytic. All compounds were initially tested at concentrations ranging from 200 to 6.25 µM against adult worms of S. mansoni parasites. The results showed the best activity of PBT2 and PBT5 at a concentration of 200 µM, which caused 100% mortality after 3 h of incubation. While at 6 h of exposure, 100% mortality was observed at the concentration of 100 µM. Subsequent studies with these same compounds allowed classifying PBT5, PBT2, PBT6 and PBT3 compounds, which were considered active and PBT1 and PBT4 compounds, which were considered inactive. In the ultrastructural analysis the compounds PBT2 and PBT5 (200 µM) promoted integumentary changes with exposure of the muscles, formation of integumentary blisters, integuments with abnormal morphology and destruction of tubercles and spicules. Therefore, the compounds PBT2 and PBT5 are promising antiparasitics against S. mansoni.


Assuntos
Esquistossomose mansoni , Esquistossomicidas , Animais , Schistosoma mansoni/ultraestrutura , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Esquistossomicidas/farmacologia , Esquistossomicidas/uso terapêutico , Antiparasitários/uso terapêutico , Esquistossomose mansoni/tratamento farmacológico , Mamíferos
3.
Chem Biol Interact ; 373: 110374, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36736872

RESUMO

BACKGROUND: ß-lapachone (ß-lap) is a naphthoquinone widely found in species of vegetables. However, its poor aqueous solubility limits its systemic administration and clinical applications in vivo. To overcome this limitation, several studies have been carried out in order to investigate techniques that can enhance the solubility and dissolution rate of ß-lap, such as the use of inclusion complexes with cyclodextrin. PURPOSE: To evaluate the in vivo effect of ß-lap complexed in methyl-ß-cyclodextrin (MßCD) on the evolutionary stages of Schistosoma mansoni in a murine model. METHODS: The development and characterization of the physicochemical properties of the inclusion complex of ß-lap in ß-lap:MßCD was prepared by solubility and dissolution tests, FTIR, DSC, X-RD and SEM. The mice were infected and subsequently treated with ß-lap:MßCD orally with 50 mg/kg/day and 100 mg/kg/day for 5 consecutive days, starting therapy on the 1st (skin schistosomula), 14th (pulmonary schistosomula), 28th (young worms) and 45th (adult worms) days after infection. Control groups were also formed; one infected untreated, treated with MßCD, and the other treated with PZQ. RESULTS: The loss of the crystalline form of ß-lap in the ß-lap:MßCD complex obtained by spray drying was proven through physical-chemical characterization analyses. ß-lap:MßCD caused reduction in the number of worms of the 33.56%, 35.7%, 35.45% and 36.45%, when the dose was at 50 mg/kg, and 65.00%, 60.34%, 52.72% and 65.01%, in the dose 100 mg/kg; when treatment was started in the 1st, 14th, 28th and 45th days after infection, respectively. It was also possible to observe a significant reduction in the number of immature eggs and an increase in the number of ripe and dead eggs and, consequently, a reduction in the damage caused by the egg antigens to the host tissue, where we attributed the reduction in the average diameter of the granulomas to the ß-lap. CONCLUSION: The dissolved content of ß-lap:MßCD by spray drying reached almost 100%, serving for future formulations and delineation of the mechanisms of action of ß-lap against S. mansoni.


Assuntos
Naftoquinonas , Schistosoma mansoni , Animais , Camundongos , Secagem por Atomização , Modelos Animais de Doenças , Naftoquinonas/farmacologia
4.
Molecules ; 27(15)2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35956946

RESUMO

Biomphalaria glabrata snails constitute the main vector of schistosomiasis in Brazil, and Bauhinia monandra Kurz, the leaves of which contain BmoLL lectin with biocidal action, is a plant widely found on continents in which the disease is endemic. This work describes the composition of B. monandra preparations and the effect on embryos and adult snails, their reproduction parameters and hemocytes. We also describe the results of a comet assay after B. glabrata exposure to sublethal concentrations of the preparations. Additionally, the effects of the preparations on S. mansoni cercariae and environmental monitoring with Artemia salina are described. In the chemical evaluation, cinnamic, flavonoid and saponin derivatives were detected in the two preparations assessed, namely the saline extract and the fraction. Both preparations were toxic to embryos in the blastula, gastrula, trochophore, veliger and hippo stages (LC50 of 0.042 and 0.0478; 0.0417 and 0.0419; 0.0897 and 0.1582; 0.3734 and 0.0974; 0.397 and 0.0970 mg/mL, respectively) and to adult snails (LC50 of 6.6 and 0.87 mg/mL, respectively), which were reproductively affected with decreased egg deposition. In blood cell analysis, characteristic cells for apoptosis, micronucleus and binucleation were detected, while for comet analysis, different degrees of nuclear damage were detected. The fraction was able to cause total mortality of the cercariae and did not present environmental toxicity. Therefore, B. monandra preparations are promising in combating schistosomiasis since they can control both the intermediate host and eliminate the infectious agent, besides being safe to the environment.


Assuntos
Bauhinia , Biomphalaria , Esquistossomose , Animais , Artemia , Folhas de Planta , Schistosoma mansoni
5.
Acta Trop ; 228: 106312, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35033504

RESUMO

This study describes for the first time the effect of saline extract and Parkia pendula seed fraction on Biomphalaria glabrata adult embryos and molluscs well as the reproductive parameters (fecundity and fertility) and survival, in addition to cytotoxicity and genotoxicity through the profile of blood cells after exposure to sublethal concentrations. Furthermore, we analyzed the action of both preparations against the cercariae of Schistosoma mansoni and their environmental safety using the bioindicator Artemia salina. The saline extract and fraction showed toxic effects for embryos (CL90 of 464.25, 479.62, 731.28, 643.28, 408.43 and 250.94, 318.03, 406.12, 635.64, 1.145 mg/mL, for blastula, gastrula, trocophore, veliger and hippo stage respectively), adult snails after 24 h of exposure (CL90 of 9.50 and 10.92 mg/mL, respectively) with increased mortality after 7 days of observation and significant decrease (p <0.05; p < 0.01 and p < 0.001) in egg mass deposition. At sublethal concentrations, an increase in quantitative and morphological changes in hemocytes was observed, and in the genotoxicity/comet assay analysis, varying degrees of nuclear damage were detected. In addition, the saline extract showed changes in the motility of the cercariae, while the fraction howed toxicity from a concentration of 1.0 mg/mL. The saline extract showed toxicity to A. salina at the highest concentrations (3.0, 4.0 and 5.0 mg/mL), while the fraction did not show ecotoxicity. Thus, the saline extract and fraction was promising in combating schistosomiasis by eliminating the intermediate host and causing alterations and/or mortality to the infectious agent.


Assuntos
Biomphalaria , Moluscocidas , Esquistossomose , Animais , Dano ao DNA , Moluscocidas/farmacologia , Extratos Vegetais/toxicidade , Schistosoma mansoni , Esquistossomose/tratamento farmacológico , Sementes
6.
Molecules ; 26(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34641539

RESUMO

Usnic acid is the best-studied lichen metabolite, presenting several biological activities, such as antibacterial, immunostimulating, antiviral, antifungal, anti-inflammatory, and antiparasitic agents; despite these relevant properties, it is a hydrophobic and toxic molecule. In this context, scientific research has driven the development of innovative alternatives, considering usnic acid as a source of raw material in obtaining new molecules, allowing structural modifications (syntheses) from it. The purpose is to optimize biological activities and toxicity, with less concentration and/or response time. This work presents a literature review with an analogy of the hydrophobic molecule of usnic acid with its hydrophilic derivative of potassium usnate, emphasizing the elucidation and structural characteristics, biological activities, and toxicological aspects of both molecules, and the advantages of using the promising derivative hydrophilic in different in vitro and in vivo assays when compared to usnic acid.


Assuntos
Benzofuranos/química , Benzofuranos/farmacologia , Potássio/química , Analgésicos/química , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antiparasitários/química , Antiparasitários/farmacologia , Benzofuranos/toxicidade , Interações Hidrofóbicas e Hidrofílicas , Líquens/metabolismo
7.
Parasite Immunol ; 43(6): e12826, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33586210

RESUMO

BACKGROUND: Extract of adult Ascaris suum (ASC) worms attenuated the liver damage in experimental autoimmune hepatitis (EAH) with induction of Th2 immune response, but fibrosis occurred. N-acetyl-L-cysteine (NAC) has protective effects against liver fibrosis. OBJECTIVES: Evaluate the association ASC + NAC on the T- and B-cell activation, inflammation and fibrogenic markers in the liver in EAH. METHODS: Experimental autoimmune hepatitis was induced intravenously with concanavalin A in BALB/c mice. EAH + ASC+NAC group received NAC and ASC; EAH + ASC group received ASC; EAH group received PBS. Doubly labelled CD4+ T (CD28, CTLA-4, CD40L or IL-10) and CD45R+ B lymphocytes (IL-10) and CD4+ CD25+ FoxP3+ cells were evaluated, along with gene expression of Col1a1, α-SMA, Fizz1, Arg1 and PPAR-γ and histomorphometry. RESULTS: Experimental autoimmune hepatitis group showed high frequency of CD28+ and CD40L+  T lymphocytes, but not the EAH + ASC group. In relation to EAH group, the Fizz1 expression was lower in both groups treated, but Arg1 expression was lower in only EAH + ASC+NAC group. In the EAH + ASC+NAC group, there were higher frequencies of CD4+ IL-10+ and CD4+ CD25+ FoxP3+ cells, but not CD45R+ IL-10+ , along with mitigated inflammation and collagen production. CONCLUSIONS: Ascaris suum favoured immunosuppression in EAH limiting the T cells activation. However, association ASC and NAC was necessary for attenuating the inflammatory process and collagen production.


Assuntos
Ascaris suum , Hepatite Autoimune , Acetilcisteína , Animais , Hepatite Autoimune/tratamento farmacológico , Imunossupressores , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais , Linfócitos T Reguladores
8.
Acta Trop ; 196: 172-179, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31082366

RESUMO

In this study, the molluscicidal activities against Biomphalaria glabrata and cercaricidal activities against Schistosoma mansoni of the ether extract of Ramalina aspera were evaluated. Additionally, toxicity parameters were evaluated at sublethal doses in terms of the influence of the extract on the fertility and fecundity of snails, as well as morphological alterations and quantification of their immunological cells. A test with Artemia salina was also carried out, in order to verify the environmental toxicity of the compound. The ether extract of R. aspera, in which divaricatic acid was identified as the major compound, demonstrated molluscicidal activity at low concentrations against both embryos (LC90 of 22.78, 24.23, 16.63 and 16.03 µg mL-1 for the gastrula, blastula, trochophore and veliger, respectively) and against adult snails (LC90 of 8.66 µg mL-1), after 24 h of exposure. At the sublethal doses, it was possible to observe a decrease in fecundity and quantitative and morphological changes in the defense cells of the exposed snails. In addition, the extract of R. aspera showed a cercaricidal effect on S. mansoni from the concentration of 5.0 µg mL-1, while showing low toxicity to Artemia salina. The ether extract of R. aspera demonstrated effective molluscicidal activity on embryos and adult snails of the species B. glabrata, cercariae of S. mansoni, and presenting low toxicity on Artemia salina. In this way, it could be considered a promising compound in the development of future molluscicidal and cercaricidal agents, thus helping to combat schistosomiasis.


Assuntos
Biomphalaria/efeitos dos fármacos , Líquens/química , Moluscocidas/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Animais , Artemia/efeitos dos fármacos , Cercárias/efeitos dos fármacos , Moluscocidas/química
9.
Rev Soc Bras Med Trop ; 52: e20180371, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30843967

RESUMO

INTRODUCTION: The levels of the full-length form of the (pro)renin receptor (PRR), a component of the renin-angiotensin system (RAS), may be reduced in the membranes of kidneys in renal diseases. This study aimed to investigate the RAS components in the kidneys of mice submitted to a combination of a high-fat diet and Schistosoma mansoni infection. METHODS: Female BALB/c mice were maintained on a control or high-fat diet from 3 weeks of age. After 10 weeks on the designated diets, half the mice in each group were infected with S. mansoni cercariae. The blood and kidneys were harvested 8 weeks after infection. RESULTS: The high-fat diet increased the number of eggs in the feces and the number of adult worms in the mesenteric bed. Schistosoma mansoni infection reduced the plasma levels of glucose, triglycerides, and HDL cholesterol in the control and high-fat diet groups. In mice on the control diet, S. mansoni infection resulted in increased expression of IL-6 in the kidneys; however, in mice on the high-fat diet, the levels of IL-6 were reduced and those of superoxide anions were increased. The RAS components evaluated were ACE2, renin, PRR, AT1R, and AT2R, and the levels of PRR were found to be reduced in the kidneys of infected mice on the high-fat diet. CONCLUSIONS: The finding regarding PRR is not yet clear. However, combining a high-fat diet and S. mansoni infection resulted in increased oxidative stress in the kidney that can aggravate hypertension as well as its associated complications.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Rim/metabolismo , Obesidade/metabolismo , Sistema Renina-Angiotensina/fisiologia , Esquistossomose mansoni/complicações , Esquistossomose mansoni/metabolismo , Actinas/análise , Animais , Glicemia/análise , Peso Corporal/fisiologia , Colesterol/sangue , Feminino , Interleucina-6/análise , Rim/fisiopatologia , Camundongos Endogâmicos BALB C , Obesidade/fisiopatologia , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Esquistossomose mansoni/fisiopatologia , Fatores de Tempo , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/análise
10.
Rev. Soc. Bras. Med. Trop ; 52: e20180371, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-990443

RESUMO

Abstract INTRODUCTION: The levels of the full-length form of the (pro)renin receptor (PRR), a component of the renin-angiotensin system (RAS), may be reduced in the membranes of kidneys in renal diseases. This study aimed to investigate the RAS components in the kidneys of mice submitted to a combination of a high-fat diet and Schistosoma mansoni infection. METHODS: Female BALB/c mice were maintained on a control or high-fat diet from 3 weeks of age. After 10 weeks on the designated diets, half the mice in each group were infected with S. mansoni cercariae. The blood and kidneys were harvested 8 weeks after infection. RESULTS: The high-fat diet increased the number of eggs in the feces and the number of adult worms in the mesenteric bed. Schistosoma mansoni infection reduced the plasma levels of glucose, triglycerides, and HDL cholesterol in the control and high-fat diet groups. In mice on the control diet, S. mansoni infection resulted in increased expression of IL-6 in the kidneys; however, in mice on the high-fat diet, the levels of IL-6 were reduced and those of superoxide anions were increased. The RAS components evaluated were ACE2, renin, PRR, AT1R, and AT2R, and the levels of PRR were found to be reduced in the kidneys of infected mice on the high-fat diet. CONCLUSIONS: The finding regarding PRR is not yet clear. However, combining a high-fat diet and S. mansoni infection resulted in increased oxidative stress in the kidney that can aggravate hypertension as well as its associated complications.


Assuntos
Animais , Feminino , Sistema Renina-Angiotensina/fisiologia , Esquistossomose mansoni/complicações , Esquistossomose mansoni/metabolismo , Dieta Hiperlipídica/efeitos adversos , Rim/metabolismo , Obesidade/metabolismo , Fatores de Tempo , Triglicerídeos/sangue , Glicemia/análise , Peso Corporal/fisiologia , Esquistossomose mansoni/fisiopatologia , Distribuição Aleatória , Colesterol/sangue , Actinas/análise , Interleucina-6/análise , Fator de Necrose Tumoral alfa/análise , Estresse Oxidativo/fisiologia , Rim/fisiopatologia , Camundongos Endogâmicos BALB C , Obesidade/fisiopatologia
11.
Data Brief ; 21: 1347-1351, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30456256

RESUMO

This text presents complementary data corresponding to schistosomiasis mansoni׳s vector control and toxicity on Schistosoma mansoni cercariae using potassium usnate. This information support our research article "Potassium Usnate Toxicity Against Embryonic Stages of the Snail Biomphalaria glabrata and Schistosoma mansoni Cercariae" [1], and focuses on the analysis of the detailed data regarding the different concentrations of potassium usnate and their efficiency to B. glabrata mortality and non-viability and S. mansoni cercariae mortality etiologic agent of the disease.

12.
Chem Biol Interact ; 283: 20-29, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29366735

RESUMO

Schistosomiasis is considered a serious public health problem in 78 countries and territories located in Africa, Asia and America and it is estimated in more than 249 million people infected by any of the species of Schistosoma. The exclusive use of praziquantel (PZQ), effective drug against all species of Schistosoma, has been the basis of the development of a possible resistance against the strains of this parasite. In addition, PZQ is not effective against young forms of worms. Thus, there is a need for the development of new drugs with schistosomicidal activity. The objective of this work was to synthesize and to evaluate the therapeutic potential of new benzodioxole derivatives (3-14) candidates for schistosomicidal drugs. All compounds synthesized showed in vitro schistosomicidal activity. The derivative 12 was considered the best compound, since it took 100% of worms to mortality in the first 72 h of exposure at the concentration of 100 µM and 83.3% at the concentration of 50 µM. Furthermore, male and female adult worms, incubated for 24 h with the compound 12 showed tegument damages characterized by extensive desquamation and edema, tuber destruction, bubble formation and exposure of the muscle layer. This compound has a restricted structure, where the thiazolidinone is attached to the 4-position of the 1,3-benzodioxol ring. The structural conformation of derivative 12 was probably responsible for the promising schistosomicidal activity, where the presence of an electron/conformational restriction of the thiazolidine ring, as well as the action of bromine as a bulk substitute, favored an increase in biological activity. In addition, tegumentary changes caused by derivative 12 may also have been responsible for the death of adult worms of Schistosoma mansoni. Therefore, we verified that the results obtained in this study make benzodioxole derivatives possible candidates for prototypes of new schistosomicidal drugs.


Assuntos
Dioxóis/química , Dioxóis/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/síntese química , Esquistossomicidas/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Dioxóis/uso terapêutico , Células HeLa , Humanos , Microscopia Eletrônica de Varredura , Praziquantel/farmacologia , Praziquantel/uso terapêutico , Schistosoma mansoni/ultraestrutura , Esquistossomose/tratamento farmacológico , Esquistossomose/patologia , Esquistossomicidas/uso terapêutico
13.
J. health sci. (Londrina) ; 18(4): http://www.pgsskroton.com.br/seer/index.php/JHealthSci/article/view/3819, 31/10/2016.
Artigo em Português | LILACS-Express | LILACS | ID: biblio-834038

RESUMO

A esplenectomia diminui a atividade de células imunes e pode estar relacionada com translocação bacteriana (TB) e sepse. Investigou-se a presença de TB e sepse em camundongos esplenectomizados, por meio de análises de peso, de sexo, de alterações da microbiota digestória e mucosa duodenal. 20 fêmeas e 20 machos de camundongos Swiss webster com 125 dias foram divididos em dois grupos: esplenectomizados e controles. Os animais foram pesados diariamente. Após sete dias da esplenectomia total convencional, os animais foram eutanasiados para estudo da TB, microbiota e morfometria intestinais. Para microbiota, foram coletadas as fezes da região média do intestino delgado, que foi seccionado para análise morfométrica. Após o preparo dos tubos com amostras fecais nas diferentes diluições, foram inoculados 0,1 mL de cada na superfície de placas contendo meios cromogênicos. Fragmentos do fígado e linfonodos mesentéricos foram macerados e homogeneizados, separadamente, em placas de Petri estéreis, posteriormente, adicionadas a caldo cérebro coração (BHI) na proporção de 1:5 e incubados em estufa a 37 °C por 24 horas. Posteriormente, alçadas de caldo foram semeadas em placas de Petri com diferentes meios de culturas. Os camundongos esplenectomizados apresentaram redução da evolução ponderal e maior prevalência de coproculturas positivas. A análise morfométrica duodenal revelou redução na altura e da área das vilosidades dos grupos esplenectomizados comparados aos seus controles. Os machos esplenectomizados apresentaram maiores taxas de TB e sepse. A asplênia aumenta a suscetibilidade à TB e, consequentemente, as doenças de origem séptica em camundongos. Sexo e alterações da mucosa duodenal podem influenciar no aumento deste fenômeno(AU)


Ssplenectomy diminishes the immune cells activity and may be related to bacterial translocation (BT) and sepsis. The BT and sepsis presence in splenectomized mice was investigated through analyzes of weight, sex, changes in the digestive microbiota and duodenal mucosa. Swiss Webster mice (20 females/20 males) were divided into two equal groups: splenectomized and controls, aged 125 days of life. Total splenectomy was performed in splenectomized group. The animals were weighed every day. After seven days, the animals were euthanized for the study of TB, microbiota and intestinal morphology. For microbiota study, stools were collected from the middle region of the small intestine, which was sectioned for morphometric analysis. After the tubes preparation with fecal samples at different dilutions, 0.1 mL of each sample was inoculated on the surface of plates containing chromogenic media. Fragments of the liver and mesenteric lymph nodes were macerated and homogenized separately in sterile Petri dishes, subsequently added to a brain/heart broth (BHI) in concentration 1:5 and incubated in an oven at 37 °C for 24 hours. Subsequently, the broths were seeded in Petri dishes with different culture media. The splenectomized mice presented a reduction in the ponderal evolution and a higher prevalence of positive coprocultures. Duodenal morphometric analysis revealed a reduction in the height and villus area of the splenectomized groups compared to their controls. Splenectomized males had higher BT and sepsis rates. Asplenia increases susceptibility to BT, and consequently septic diseases in mice. Sex and duodenal mucosa alterations may influence the increase of this phenomenon.(AU)

14.
Exp Parasitol ; 142: 83-90, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24768955

RESUMO

The present study provides, for the first time, conclusions on the in vitro schistosomicidal properties of ß-lap. Adult male Schistosoma mansoni worms of the BH strain were used for the study. Motility, mortality, cell viability and alterations in the tegument were employed as schistosomicidal parameters. Alterations in motility were observed 6h after incubation in concentrations of 50 and 100 µM. ß-lap decreased significantly the worm viability, reducing the formation of formazan in 17.7%, 27.4% and 54.8% at concentrations of 25, 50 and 100 µM, respectively. Mortality in concentrations of 50 and 100 µM was of 67% and 100%, respectively, after 24h. The death of the parasite was preceded by progressive surface membrane damage, characterized by tegument peeling, spine reduction and erosion, blister formation and rupture, and the emergence of holes. In addition to this, in the anterior portion, intense general edema, areas of cracking with a wrinkled surface, furrows and a fibrous appearance were also observed. The results of the present study thus provide a sound basis for further in-depth studies of the schistosomicidal properties of ß-lap, both in the laboratory and in the field.


Assuntos
Naftoquinonas/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/farmacologia , Animais , Masculino , Camundongos , Microscopia Eletrônica de Varredura , Movimento/efeitos dos fármacos , Naftoquinonas/química , Praziquantel/farmacologia , Schistosoma mansoni/fisiologia , Schistosoma mansoni/ultraestrutura , Esquistossomicidas/química
15.
Phytomedicine ; 21(3): 261-7, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24090700

RESUMO

The activity of ß-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione, ß-lap) against different stages of Schistosoma mansoni was investigated in mice. Mice infected with 50 cercariae (BH strain) were intraperitoneally treated at a dose of 50 mg/kg for 5 consecutive days, starting on the 1st, 14th, 28th and 45th days after infection, to evaluate the effect of ß-lap on skin schistosomula, lung schistosomula, young worms (before oviposition) and adult worms (after oviposition), respectively. All animals were euthanized 60 days after infection. ß-Lap significantly reduced (p<0.001) the number of worms in 29.78%, 37.2%, 24.2% and 40.22% when administered during the phases of skin schistosomula, lung schistosomula, young worms and adult worms, respectively. Significant reduction was also achieved in terms of female burden. In all groups, there was significant reduction in the number of eggs and granulomas in the hepatic tissue. When the intervention was performed during the phase of adult worms, ß-lap reduced the size of hepatic granulomas and changed the oogram pattern, lowering the percentage of immature eggs and increasing the percentage of mature and dead eggs. Our data indicate that ß-lap has moderate antischistosomal properties. Its molecule may also be used as a prototype for synthesis of new naphthoquinone derivatives with potential schistosomicidal properties. Further studies with different formulations containing ß-lap are needed to clearly establish the best dose and route of administration and its mechanism of action against schistosomes.


Assuntos
Hepatopatias/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Naftoquinonas/uso terapêutico , Fitoterapia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Animais , Antiparasitários/farmacologia , Antiparasitários/uso terapêutico , Feminino , Granuloma , Estágios do Ciclo de Vida , Fígado/parasitologia , Hepatopatias/parasitologia , Hepatopatias/patologia , Pulmão/parasitologia , Pneumopatias/parasitologia , Magnoliopsida/química , Camundongos , Naftoquinonas/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Schistosoma mansoni/crescimento & desenvolvimento , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/patologia , Pele/parasitologia , Dermatopatias/parasitologia
16.
Acta Gastroenterol Latinoam ; 42(4): 309-20, 2012 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-23383525

RESUMO

INTRODUCTION: Schistosomiasis causes alterations of the intestinal mucosa and a low cellular immune response in its chronic phase. Gender may influence the inflammatory response against Schistosoma mansoni. We investigate the association between schistosomiasis and secondary infections by bacterial translocation. METHODS: Swiss Webster mice (Mus musculus) with 35 days were divided into two groups: control (10 male and 10 female) and schistosomiasis (10 male and 10 female infected with 50 cercariae percutaneously). Stools were examined by the Kato-Katz with 45 and 97 days of infection. Liver perfusion was performed for quantification of worms. The animals were weighed after 35, 80, 125 and 132 days old when they were euthanized for study of translocation, microbiota and duodenal mucosa. For microbiota, stools were collected from the middle of the small intestine. Segments of this region were sectioned for morphometric diagnosis. RESULTS: Females had higher schistosomotic number of adult worms and eggs in stools (P = 0. 0001). Both sexes had a higher number of eggs on the 45th day (P = 0.005), decreased weight gain with 80, 125 and 132 days old (P = 0.0001) and increased spleen weight (P = 0.0001). The animals with schistosomiasis had more bacterial species and colony-forming units. Morphometric analysis revealed a reduction in height and area of villus and of perimeter of the mucosal surface of both groups with chronic disease (P = 0.0001). Increased bacterial translocation occurred in schistosomiasis when compared to controls, being more prevalent in females. CONCLUSIONS: Chronic schistosomiasis modify weight gain and weight of spleen, duodenal mucosa and microbiota in mice and favors translocation, migration and sepsis, especially in females, probably due to the intensity of parasitism.


Assuntos
Translocação Bacteriana/fisiologia , Duodeno/microbiologia , Mucosa Intestinal/microbiologia , Esquistossomose mansoni/microbiologia , Animais , Peso Corporal , Doença Crônica , Fezes/parasitologia , Feminino , Masculino , Camundongos , Contagem de Ovos de Parasitas , Esquistossomose mansoni/fisiopatologia , Fatores Sexuais , Fatores de Tempo
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