RESUMO
Cutaneous secretions of amphibians have bioactive compounds, such as peptides, with potential for biotechnological applications. Therefore, this study aimed to determine the primary structure and investigate peptides obtained from the cutaneous secretions of the amphibian, Leptodactylus vastus, as a source of bioactive molecules. The peptides obtained possessed the amino acid sequences, GVVDILKGAAKDLAGH and GVVDILKGAAKDLAGHLASKV, with monoisotopic masses of [M + H]± = 1563.8 Da and [M + H]± = 2062.4 Da, respectively. The molecules were characterized as peptides of the class of ocellatins and were named as Ocellatin-K1(1-16) and Ocellatin-K1(1-21). Functional analysis revealed that Ocellatin-K1(1-16) and Ocellatin-K1(1-21) showed weak antibacterial activity. However, treatment of mice with these ocellatins reduced the nitrite and malondialdehyde content. Moreover, superoxide dismutase enzymatic activity and glutathione concentration were increased in the hippocampus of mice. In addition, Ocellatin-K1(1-16) and Ocellatin-K1(1-21) were effective in impairing lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) formation and NF-kB activation in living microglia. We incubated hippocampal neurons with microglial conditioned media treated with LPS and LPS in the presence of Ocellatin-K1(1-16) and Ocellatin-K1(1-21) and observed that both peptides reduced the oxidative stress in hippocampal neurons. Furthermore, these ocellatins demonstrated low cytotoxicity towards erythrocytes. These functional properties suggest possible to neuromodulatory therapeutic applications.
Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Anuros/metabolismo , Hipocampo/efeitos dos fármacos , Infecções/tratamento farmacológico , Neurônios/efeitos dos fármacos , Sequência de Aminoácidos/genética , Animais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Hipocampo/metabolismo , Infecções/induzido quimicamente , Infecções/genética , Infecções/microbiologia , Lipopolissacarídeos/toxicidade , Camundongos , Microglia/efeitos dos fármacos , NF-kappa B/genética , Neurônios/metabolismo , Nitritos/antagonistas & inibidores , Nitritos/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Anadenanthera colubrina var. cebil (Griseb.) Altschul (Fabaceae family), commonly known as the red angico tree, is a medicinal plant found throughout Brazil's semi-arid area. In this study, a chemical analysis was performed to investigate the antidiarrheal activity and safety profile of red angico gum (RAG), a biopolymer extracted from the trunk exudate of A. colubrina. Upon FT-IR spectroscopy, RAG showed bands in the regions of 1608 cm-1, 1368 cm-1, and 1029 cm-1, which relate to the vibration of O-H water molecules, deformation vibration of C-O bands, and vibration of the polysaccharide C-O band, respectively, all of which are relevant to glycosidic bonds. The peak molar mass of RAG was 1.89 × 105 g/mol, with the zeta potential indicating electronegativity. RAG demonstrated high yield and solubility with a low degree of impurity. Pre-treatment with RAG reduced the total diarrheal stool and enteropooling. RAG also enhanced Na+/K+-ATPase activity and reduced gastrointestinal transit, and thereby inhibited intestinal smooth muscle contractions. Enzyme-Linked Immunosorbent Assay (ELISA) demonstrated that RAG can interact with GM1 receptors and can also reduce E. coli-induced diarrhea in vivo. Moreover, RAG did not induce any signs of toxicity in mice. These results suggest that RAG is a possible candidate for the treatment of diarrheal diseases.
RESUMO
This study aimed to evaluate the effect of Lactobacillus reuteri DSM 17938 (DSM) on ethanol-induced gastric injury, and if its possible mechanism of action is related to inhibiting the transient receptor potential vanilloid type 1 (TRPV1). We evaluated the effect of supplementing 108 CFUâ¢g body wt-1â¢day-1 of DSM on ethanol-induced gastric injury. DSM significantly reduced the ulcer area (1.940 ± 1.121 mm²) with 3 days of pretreatment. The effects of DSM supplementation were reversed by Resiniferatoxin (RTX), TRPV1 agonist (3 nmol/kg p.o.). Substance P (SP) (1 µmol/L per 20 g) plus 50% ethanol resulted in hemorrhagic lesions, and DSM supplementation did not reverse the lesion area induced by administering SP. TRPV1 staining intensity was lower, SP, malondialdehyde (MDA) and nitrite levels were reduced, and restored normal levels of antioxidant parameters (glutathione and superoxide dismutase) in the gastric mucosa in mice treated with DSM. In conclusion, DSM exhibited gastroprotective activity through decreased expression of TRPV1 receptor and decreasing SP levels, with a consequent reduction of oxidative stress.
Assuntos
Etanol/efeitos adversos , Mucosa Gástrica/patologia , Limosilactobacillus reuteri/crescimento & desenvolvimento , Probióticos/uso terapêutico , Úlcera Gástrica/prevenção & controle , Substância P/antagonistas & inibidores , Canais de Cátion TRPV/antagonistas & inibidores , Animais , Antioxidantes/metabolismo , Diterpenos/farmacologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/induzido quimicamente , Gastrite/metabolismo , Gastrite/prevenção & controle , Glutationa/metabolismo , Limosilactobacillus reuteri/classificação , Malondialdeído/metabolismo , Camundongos , Substâncias Protetoras/uso terapêutico , Especificidade da Espécie , Estômago/microbiologia , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo , Canais de Cátion TRPV/farmacologiaRESUMO
Hydrogen sulphide (H2S) is a gasotransmitter that participates in various physiological and pathophysiological processes within the gastrointestinal tract. We studied the effects and possible mechanism of action of H2S in secretory diarrhoea caused by cholera toxin (CT). The possible mechanisms of action of H2S were investigated using an intestinal fluid secretion model in isolated intestinal loops on anaesthetized mice treated with CT. NaHS and Lawesson's reagent and l-cysteine showed antisecretory activity through reduction of intestinal fluid secretion and loss of Cl- induced by CT. Pretreatment with an inhibitor of cystathionine-γ-lyase (CSE), dl-propargylglycine (PAG), reversed the effect of l-cysteine and caused severe intestinal secretion. Co-treatment with PAG and a submaximal dose of CT increased intestinal fluid secretion, thus supporting the role of H2S in the pathophysiology of cholera. CT increased the expression of CSE and the production of H2S. Pretreatment with PAG did not reverse the effect of SQ 22536 (an AC inhibitor), bupivacaine (inhibitor of cAMP production), KT-5720 (a PKA inhibitor), and AICAR (an AMPK activator). The treatment with Forskolin does not reverse the effects of the H2S donors. Co-treatment with either NaHS or Lawesson's reagent and dorsomorphin (an AMPK inhibitor) did not reverse the effect of the H2S donors. H2S has antisecretory activity and is an essential molecule for protection against the intestinal secretion induced by CT. Thus, H2S donor drugs are promising candidates for cholera therapy. However, more studies are needed to elucidate the possible mechanism of action.
Assuntos
Toxina da Cólera/antagonistas & inibidores , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Sulfeto de Hidrogênio/farmacologia , Transdução de Sinais , Proteínas Quinases Ativadas por AMP/metabolismo , Adenilil Ciclases/metabolismo , Animais , Toxina da Cólera/farmacologia , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Feminino , Masculino , CamundongosRESUMO
Inflammation is a protective reaction of the microcirculation. However, sustained inflammation can lead to undesired effects. Thuja occidentalis Linn has many pharmacological properties but has no anti-inflammatory activity described. Thus, this study aims evaluating the anti-inflammatory activity of the aqueous extract (AE) and the polysaccharide fraction (PLS) of T. occidentalis L. in mice. The results of our evaluations in various experimental models indicated that AE and PLS (3, 10, and 30mg/kg, i.p.) reduced (pË0.05) paw edema induced by carrageenan, dextran sulfate (DEX), compound 48/80, serotonin (5-HT), bradykinin (BK), histamine (HIST), and prostaglandin E2 (PGE2). Furthermore, it inhibited neutrophils recruitment; decreased MPO activity, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, vascular permeability, nitrite concentration, and MDA concentration; and maintained the GSH levels in the peritoneal exudate. The AE and PLS reduced neutrophil infiltration and cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) immunostaining in paw tissue. Treatment with the AE and PLS (300mg/kg) did not induce gastric toxicity. In conclusion, these results show that the AE and PLS reduced the inflammatory response by inhibiting vascular and cellular events, inhibiting pro-inflammatory cytokine production, and reducing oxidative stress. Furthermore, they did not induce gastric toxicity at high doses.
Assuntos
Anti-Inflamatórios/farmacologia , Polissacarídeos/farmacologia , Thuja/química , Água/química , Animais , Anti-Inflamatórios/uso terapêutico , Permeabilidade Capilar/efeitos dos fármacos , Edema/tratamento farmacológico , Edema/metabolismo , Glutationa/metabolismo , Interleucina-6/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Cavidade Peritoneal , Peritonite/tratamento farmacológico , Peroxidase/metabolismo , Polissacarídeos/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Hydrogen sulfide (H2S) is a signaling molecule in the gastrointestinal tract. H2S production can derive from d-cysteine via various pathways, thus pointing to a new therapeutic approach: delivery of H2S to specific tissues. This study was designed to evaluate the concentration and effects of H2S (generated by d-amino acid oxidase [DAO] from d-cysteine) in the gastric mucosa and the protective effects against ethanol-induced lesions in mice. Mice were treated with l-cysteine or d-cysteine (100 mg/kg per os). Other groups received oral l-propargylglycine (cystathionine γ-lyase inhibitor, 100 mg/kg) or indole-2-carboxylate (DAO inhibitor), and 30 min later, received d- or l-cysteine. After 30 min, 50% ethanol (2.5 mL/kg, per os) was administered. After 1 h, the mice were euthanized and their stomachs excised and analyzed. Pretreatment with either l-cysteine or d-cysteine significantly reduced ethanol-induced lesions. Pretreatment of d-cysteine- or l-cysteine-treated groups with indole-2-carboxylate reversed the gastroprotective effects of d-cysteine but not l-cysteine. Histological analysis revealed that pretreatment with d-cysteine decreased hemorrhagic damage, edema, and the loss of the epithelium, whereas the administration of indole-2-carboxylate reversed these effects. d-Cysteine also reduced malondialdehyde levels but maintained the levels of reduced glutathione. Furthermore, pretreatment with d-cysteine increased the synthesis of H2S. Thus, an H2S-generating pathway (involving d-cysteine and DAO) is present in the gastric mucosa and protects this tissue from ethanol-induced damage by decreasing direct oxidative damage.
Assuntos
Antioxidantes/farmacologia , Cisteína/farmacologia , D-Aminoácido Oxidase/metabolismo , Mucosa Gástrica , Sulfeto de Hidrogênio/metabolismo , Animais , Etanol/efeitos adversos , Feminino , Mucosa Gástrica/química , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Glutationa/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Gastropatias/induzido quimicamente , Gastropatias/metabolismoRESUMO
Sulphated polysaccharides extracted from algae have been extensively studied for their diverse biological activities. Thus, the purpose of this study was to evaluate the chemical composition, the anti-diarrhoeal effect and acute toxicity of a sulphated polysaccharide fraction obtained from Gracilaria intermedia (SP-Gi). Initially, the FT-IR of SP-Gi revealed to be an agaran with sulphation at C-6 of the l-galactosyl residues. The anti-diarrhoeal activity of SP-Gi was evaluated in a castor oil-induced diarrhoea model. The effects of SP-Gi on enteropooling, Na +-K +-ATPase activity, gastrointestinal transit, and gastric emptying were then examined. Subsequently, the effect of SP-Gi on diarrhoea induced by cholera toxin (CT) and Escherichia coli was examined. In addition, an acute toxicity test was conducted in accordance with OECD guideline 423. Pre-treatment with SP-Gi reduces the total faeces, total diarrhoeal faeces, and enteropooling. SP-Gi (30mg/kg p.o.) increased Na+/K+-ATPase activity and reduced gastrointestinal transit through anticholinergic mechanisms. ELISA demonstrated that SP-Gi can interact with GM1 receptors and CT. SP-Gi reduced diarrhoea induced by E. coli and prevented weight loss in the animals. Moreover, SP-Gi did not induce any toxicity signs. These results suggest that SP-Gi is a possible candidate for the treatment of diarrhoeal illnesses.
Assuntos
Diarreia/tratamento farmacológico , Gracilaria/química , Polissacarídeos/efeitos adversos , Polissacarídeos/farmacologia , Segurança , Sulfatos/química , Animais , Óleo de Rícino/farmacologia , Diarreia/induzido quimicamente , Diarreia/fisiopatologia , Escherichia coli/efeitos dos fármacos , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Intestinos/fisiopatologia , Masculino , Camundongos , Polissacarídeos/química , Polissacarídeos/uso terapêuticoRESUMO
ß-Caryophyllene (BCP) is a sesquiterpene that shows high potential in pharmacological applications. However, these have been drastically limited by the respective volatility and poor water solubility. The present study investigates the formation of inclusion complexes between BCP and methyl-ß-cyclodextrin (MßCD) and shows that these complexes promote a significant improvement of the anti-inflammatory, gastric protection, and antioxidant activities relative to neat BCP. It is shown that the solubility of BCP is significantly increased through complexation in phase solubility studies. Inclusion complexes with MßCD in solid state were prepared by three different methods, kneading, rotary evaporation, and lyophilization, with the latter confirmed by differential scanning calorimetry, Fourier transformed infrared spectroscopy, scanning electron microscopy, 1H NMR spectroscopy, and molecular dynamics studies. This study provides for the first time a full characterization of inclusion complexes between BCP and MßCD and highlights the impact of complex formation upon pharmacological activity.
RESUMO
Intestinal mucositis is an inflammatory process occurring in the intestinal mucosa and is a common side effect of irinotecan hydrochloride (CPT-11) based anticancer regimens. The transient receptor potential cation channel, subfamily A, member 1 (TRPA1) receptor is highly expressed in the intestinal mucosa and has the ability to identify cell damage signaling indicates its possible association with intestinal mucositis. Carvacrol is an agonist of the TRPA1 receptor and has anti-inflammatory properties. Thus, the aim of the present study was to verify the supposed anti-inflammatory and protective action of carvacrol via TRPA1 activation against intestinal mucositis induced by CPT-11 in mice. Briefly, mice were treated with either DMSO 2% or CPT-11 (75 mg/kg, per 4 days, i.p.) or the carvacrol (25, 75 or 150 mg/kg, per 8 days, i.p.) before CPT-11. In other group, the animals were pretreated with HC-030031, a TRPA1 antagonist, 30 min before treatment with carvacrol. On day 7, animal survival and bacteremia were assessed, and following euthanasia, samples of the jejunum were obtained for morphometric analysis and measurement of antioxidant and pro-inflammatory markers. Carvacrol was found to exert an anti-inflammatory action against CPT-11-induced intestinal mucositis through strong interactions with TRPA1 receptors; reduction in the production or release or both of pro-inflammatory cytokines (TNF-α, IL-1ß, and KC); and decrease in other indicators of inflammation (MPO, NF-κB, COX-2) and oxidative stress (GSH, MDA, and NOx levels). It also contributed to the restoration of the tissue architecture of the villi and crypts in the small intestine, and improved clinical parameters such as survival, body mass variation, leukogram, and blood bacterial count. Thus, TRPA1 could be a target for future therapeutic approaches in the treatment of intestinal mucositis.
Assuntos
Camptotecina/análogos & derivados , Inflamação/tratamento farmacológico , Intestinos/patologia , Monoterpenos/uso terapêutico , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Estresse Oxidativo , Canais de Potencial de Receptor Transitório/metabolismo , Animais , Antioxidantes/metabolismo , Peso Corporal/efeitos dos fármacos , Camptotecina/efeitos adversos , Ciclo-Oxigenase 2/metabolismo , Cimenos , Feminino , Imuno-Histoquímica , Inflamação/sangue , Inflamação/complicações , Intestinos/efeitos dos fármacos , Intestinos/enzimologia , Irinotecano , Contagem de Leucócitos , Camundongos , Simulação de Acoplamento Molecular , Monoterpenos/química , Monoterpenos/farmacologia , Mucosite/sangue , Mucosite/enzimologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Análise de Sobrevida , Canal de Cátion TRPA1 , Canais de Potencial de Receptor Transitório/agonistasRESUMO
BACKGROUND: Attention to prenatal care and child delivery is important for the health of women and children, but in the Amazon these indicators tend to be historically unfavorable, in part by geographical and political isolation. In 2003 both Brazilian and Peru governments have finished paving an international road connecting remotes areas in the Brazilian Amazon to the Pacific coast in Peru. METHODS: The situation of prenatal care and child delivery with mothers of children under 5 years old living in the urban area of Assis Brasil, Acre was assessed in two cross-sectional studies performed in 2003 and 2011, corresponding to the period before and after the Pacific highway construction. RESULTS: In 2003, most mothers were of black/Afro-American ethnicity, or "pardos" (the offspring of a Caucasian with a African descendant) (77.69 %), had more than 4 years of schooling (73.40 %) and had a mean age of 22.18 years. In 2011, the number of as a migration of indigenous women increased from 0 to 14.40 % of the respondents, because of migration from communities along the rivers to urban areas, with no other significant changes in maternal characteristics. No significant improvement in childbirth assistance was noticed between 1997 and 2011; only the percentage of in-hospital vaginal deliveries performed by doctors increased from 17.89 to 66.26 % (p <0.001) during this period. Access to prenatal care was associated with white ethnicity in 2003, and higher socioeconomic level and white ethnicity in 2011, while the higher number of prenatal visits was associated with higher maternal education and higher socioeconomic levels in 2011. Vaginal child delivery at a hospital facility was associated with maternal age in 2003, and year of birth, being of white ethnicity and higher level of education in 2011. CONCLUSIONS: The indicators of prenatal care and child delivery were below the national average, showing that geographical isolation still affects women's health care in the Amazon, despite the construction of the highway and governmental health protocols adopted during this period.
Assuntos
Parto Obstétrico/métodos , Acessibilidade aos Serviços de Saúde/normas , Cuidado Pré-Natal/estatística & dados numéricos , Adulto , Brasil , Indústria da Construção , Estudos Transversais , Parto Obstétrico/normas , Parto Obstétrico/estatística & dados numéricos , Etnicidade/psicologia , Etnicidade/estatística & dados numéricos , Feminino , Acessibilidade aos Serviços de Saúde/tendências , Humanos , GravidezRESUMO
The angiotensin (Ang) II converting enzyme (ACE II) pathway has recently been shown to be associated with several beneficial effects in various organisms, including gastroprotection. ACE II is responsible for converting Ang II into an active peptide, Ang-(1-7), which in turn binds the Mas receptor. Recent studies have shown that diminazene aceturate (Dize) a trypanocidal used in animals, activates ACE II. Thus, in this study, we aimed to evaluate the gastroprotective effects of Dize via the ACE II/Ang-(1-7)/Mas receptor pathway against gastric lesions induced by ethanol and acetic acid in mice. The results showed that Dize could promote gastric protection via several mechanisms, including increased levels of antioxidants and anti-inflammatory factors (e.g., decreasing tumor necrosis factor and interleukin-6 expression and reducing myeloperoxidase activity), maturation of collagen fibers, and promotion of re-epithelialization and regeneration of gastric tissue in different injury models. Thus, Dize represents a novel potential gastroprotective agent.
Assuntos
Angiotensina I/metabolismo , Diminazena/análogos & derivados , Mucosa Gástrica/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ácido Acético/administração & dosagem , Enzima de Conversão de Angiotensina 2 , Animais , Diminazena/farmacologia , Diminazena/uso terapêutico , Modelos Animais de Doenças , Etanol/administração & dosagem , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Masculino , Camundongos , Proto-Oncogene Mas , Sistema Renina-Angiotensina/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Úlcera Gástrica/prevenção & controleRESUMO
Seaweeds are sources of diverse bioactive compounds, such as sulphated polysaccharides. This study was designed to evaluate the chemical composition and anti-diarrheal activity of a fraction of sulphated polysaccharide (PLS) obtained from the red seaweed Hypnea musciformis in different animal models, and to elucidate the underlying mechanisms. PLS was obtained by aqueous extraction, with a yield of 31.8% of the seaweed dry weight. The total carbohydrate content accounted for 99% of the sample. The sulfate content of the polysaccharide was 5.08% and the percentage of carbon was 25.98%. Pretreatment with all doses of PLS inhibited castor oil-induced diarrhea, with reduction of the total amount of stool, diarrheal stools, and the severity of diarrhea. PLS (90 mg/Kg) decreased castor oil- and PGE2-induced enteropooling. In addition, PLS (90 mg/Kg) increased the Na(+)/K(+)-ATPase activity in the small intestine and reduced gastrointestinal transit, possibly via activation of cholinergic receptors. Interestingly, the cholera toxin-induced fluid secretion and Cl(-) ion levels decreased in the intestinal contents of the animals pretreated with PLS (90 mg/kg), probably via reduction of toxin-GM1 receptor binding. In conclusion, PLS exerts anti-diarrheal activity by increasing Na(+)/K(+)-ATPase activity, inhibiting gastrointestinal motility, and blocking the toxin-GM1 receptor binding.
Assuntos
Diarreia/tratamento farmacológico , Polissacarídeos/química , Polissacarídeos/farmacologia , Rodófitas/química , Sulfatos/química , Animais , Óleo de Rícino/efeitos adversos , Toxina da Cólera/toxicidade , Diarreia/induzido quimicamente , Diarreia/metabolismo , Diarreia/fisiopatologia , Feminino , Trânsito Gastrointestinal/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/fisiopatologia , Masculino , Camundongos , Antagonistas de Entorpecentes/farmacologia , Polissacarídeos/uso terapêutico , Ratos , Receptores de Superfície Celular/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
Diarrhoea is a significant health problem for children in developing countries that causes more than 1 million deaths annually. This study aimed to evaluate the antidiarrhoeal effect of sulphated polysaccharide (PLS) from the alga Gracilaria caudata in rodents. For the evaluation, acute diarrhoea was induced in Wistar rats (150-200 g) by administration of castor oil (10 mg/kg). Then, different parameters, including enteropooling and gastrointestinal transit and its pharmacological modulation by opioid and cholinergic pathways, were assessed using activated charcoal in Swiss Mice (25-30 g). Secretory diarrhoea was examined using cholera toxin (CT) (1 mg/loop)-treated, isolated intestinal loops from Swiss mice (25-30 g), which were also used to examine fluid secretion, loss of chloride ions into the intestinal lumen and absorption. In addition, a GM1-dependent ELISA was used to evaluate the interaction between PLS, CT and the GM1 receptor. Pre-treatment with PLS (10, 30 and 90 mg/kg) reduced faecal mass, diarrhoeal faeces and enteropooling. However, 90 mg/kg more effectively reduced these symptoms; therefore, it was used as the standard dose in subsequent experiments. Gastrointestinal transit was also reduced by PLS treatment via a cholinergic mechanism. Regarding the diarrhoea caused by CT, PLS reduced all study parameters, and the ELISA showed that PLS can interact with both the GM1 receptor and CT. These results show that PLS from G. caudata effectively improved the parameters observed in acute and secretory diarrhoea, which affects millions of people, and may lead to the development of a new alternative therapy for this disease.
Assuntos
Antidiarreicos/uso terapêutico , Diarreia/tratamento farmacológico , Gracilaria/química , Fitoterapia/métodos , Polissacarídeos/farmacologia , Alga Marinha/química , Animais , Brasil , Óleo de Rícino/farmacologia , Catárticos/farmacologia , Toxina da Cólera/farmacologia , Diarreia/induzido quimicamente , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Trânsito Gastrointestinal/efeitos dos fármacos , Camundongos , Ratos , Ratos Wistar , Receptores de Superfície Celular/metabolismoRESUMO
BACKGROUND: It has been reported that simvastatin, a statin commonly prescribed for its anti-inflammatory and antioxidant effects, has gastroprotective effects in indomethacin and ethanol-induced gastric ulcers. However, the effects of simvastatin on alendronate-induced gastric mucosal injury remain unexplored. AIM: This study investigated the use of simvastatin for the treatment of alendronate-induced gastric ulcers in rats. METHODS: Female rats were pretreated with vehicle or simvastatin (20 and 60 mg/kg p.o.). After 1 h, the rats received alendronate (50 mg/kg p.o.). Simvastatin was administered once daily for 7 days, and from the fourth day of simvastatin treatment, alendronate was administered once daily for 4 days. On the final day of treatment, 4 h after alendronate administration, animals were euthanized, their stomachs were removed, and gastric damage was measured. Samples of the stomach were fixed in 10 % formalin immediately after their removal for subsequent histopathological assessment. Unfixed samples were weighed, frozen at -80 °C until assayed for glutathione (GSH), malondialdehyde (MDA), and cytokine levels and myeloperoxidase (MPO) activity. A third group was used to measure mucus and gastric secretion. RESULTS: Pretreatment with simvastatin prevented alendronate-induced macroscopic gastric damage and reduced the levels of MDA and GSH, TNF-α and IL-1ß, MPO activity, and mucus levels, in the stomach. CONCLUSIONS: This study demonstrates the protective effects of simvastatin against alendronate-induced gastric ulceration. Maintenance of mucosal integrity, inhibition of neutrophil activity, and reduced oxidative stress associated with decreased gastric acidity may explain the gastroprotective effects of simvastatin.
Assuntos
Alendronato/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Sinvastatina/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Animais , Conservadores da Densidade Óssea/toxicidade , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Malondialdeído/metabolismo , Peroxidase/genética , Peroxidase/metabolismo , Ratos , Ratos Wistar , Sinvastatina/administração & dosagem , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: The Amazon region has the highest seroprevalence of hepatitis A virus (HAV) in Brazil. METHODS: In the present study, the seroprevalence of total HAV antibodies in two groups, composed of 147 and 254 children between 1 and 5 years old in Assis Brasil, Acre, was measured in 2003 and 2010, respectively, and compared with socio-economic changes in the city. RESULTS: In 2003, the HAV seroprevalence rate was 26.5%, while in 2010, it was 22.4%. There was an overall improvement in socio-economic and sanitary conditions, with the exception of open sewage. In 2003, factors associated with positive serology were child age (aOR [adjusted odds ratio] 1.84; 95% CI: 1.28-2.64), having a latrine or not having a toilet at home (aOR 4.73; 95% CI: 1.06-21.17) and the treatment of drinking water with chlorine (aOR 0.26; 95% CI: 0.07-0.92). In 2010, the main factors associated with positive serology were using rivers, streams and rainwater as sources of water for domestic purposes (aOR 24.36; 95% CI: 3.69-160.85); having a wooden or ground floor at home (OR 2.51; 95% CI: 1.11-5.69) and child age (aOR 2.33; 95% CI: 1.66-3.28). CONCLUSIONS: In the Brazilian Amazon, sanitation and water treatment still require improvement and socio-economic development is warranted in order to decrease hepatitis A transmission.
Assuntos
Hepatite A/epidemiologia , Distribuição por Idade , Brasil/epidemiologia , Pré-Escolar , Água Potável , Feminino , Anticorpos Anti-Hepatite A/sangue , Humanos , Lactente , Masculino , Razão de Chances , Saneamento , Estudos Soroepidemiológicos , Fatores SocioeconômicosRESUMO
BACKGROUND: Hepatitis A is still a neglected health problem in the world. The most affected areas are the ones with disadvantaged socioeconomic conditions. In Brazil, seroprevalence studies showed that 64.7 % of the general population has antibodies against HAV (hepatitis A virus), and the Amazon region has the highest seroprevalence in the country. METHODS: In the present study the seroprevalence of total HAV antibodies in children between 1 and 5 years old residing in the urban area of Assis Brasil, Acre was measured and spatial distribution of several socioeconomic inequities was evaluated. RESULTS: In the year of 2011, seroprevalence rate was 16.66 %. Factors associated with having a positive serology identified by multivariate analysis were being of indigenous ethnicity [adjusted Odds Ratio (aOR) = 3.27, CI 1.45-7.28], usage of water from the public system (aOR = 8.18, CI 1.07-62.53), living in a house not located in a street (aOR = 3.48, CI 1.54-7.87), and child age over 4 years old (aOR = 2.43, CI 1.23-4.79). The distribution of seropositive children was clustered in the eastern part of the city, where several socioeconomic inequities (lack of flushed toilets, lack of piped water inside the household and susceptibility of the household to flooding during rain, low maternal education, having wood or ground floor at home, and not owning a house, lack of piped water at home, and type of drinking water) also clustered. CONCLUSIONS: The findings highlight that sanitation and water treatment still need improvement in the Brazilian Amazon, and that socioeconomic development is warranted in order to decrease this and other infectious diseases.
Assuntos
Hepatite A/diagnóstico , Fatores Socioeconômicos , Brasil/epidemiologia , Pré-Escolar , Estudos Transversais , Demografia , Feminino , Hepatite A/epidemiologia , Hepatite A/virologia , Anticorpos Anti-Hepatite A/sangue , Vírus da Hepatite A/isolamento & purificação , Humanos , Lactente , Masculino , Análise Multivariada , Razão de Chances , Prevalência , Fatores de RiscoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Anacardium occidentale L. (Anacardiaceae) is commonly known as the cashew tree. It is native to tropical America and extracts of the leaves, bark, roots, chestnut net and exudate have been traditionally used in northeast Brazil for the treatment of various diseases. The exudate of the cashew tree (cashew gum) has been exploited by locals since ancient times for multiple applications, including the treatment of diarrheal diseases. AIM OF THE STUDY: The primary aim of the present study is to evaluate the antidiarrheal activity of cashew gum (CG), a complex heteropolysaccharide from the exudate of the cashew tree, using various models. MATERIALS AND METHODS: The antidiarrheal activity of cashew gum (CG) against acute diarrhea was investigated using the castor oil-induced diarrhea model. The effects of CG on gastrointestinal transit and castor oil- and PGE2- induced enteropooling were also examined in rodents. In addition, the effect of CG against secretory diarrhea was investigated using a model of fluid secretion in cholera toxin-treated intestinal closed loops in live mice. RESULTS: Cashew gum (30, 60, and 90 mg/kg, p.o.) showed a significant (P<0.05-0.01) antidiarrheal effect in rats with castor oil-induced diarrhea, inhibiting the total amount of stool and diarrheal stools. The 60 mg/kg dose of CG exhibited excellent antidiarrheal activity and significantly reduced the severity of diarrhea (diarrhea scores) in rats. CG (60 mg/kg) significantly (P<0.05) decreased the volume of castor oil- and PGE2-induced intestinal fluid secretion (enteropooling). In addition, similar to loperamide (standard drug, 5 mg/kg, p.o.), CG treatment reduced the distance traveled by a charcoal meal in the 30-min gastrointestinal transit model by interacting with opioid receptors. In cholera toxin-induced secretory diarrhea, CG (60 mg/kg) significantly inhibited the intestinal fluid secretion and decreased Cl(-) ion loss in the cholera toxin(-)treated isolated loops model of live mice by competitively binding to cholera toxin-GM1 receptors. CONCLUSIONS: In conclusion, our results indicate that a complex heteropolysaccharide extracted from the exudate of A. occidentale L. has antidiarrheal activity in acute, inflammatory, and secretory diarrhea models, which could justify its traditional use in the treatment of diarrhea in northeast Brazil. The antidiarrheal activity might be explained by the capacity of CG to inhibit gastrointestinal motility and thereby reduce the accumulation of intestinal fluid and the secretion of water and chloride ions in the lumen of the intestine.
Assuntos
Anacardium , Antidiarreicos/uso terapêutico , Diarreia/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Gomas Vegetais/uso terapêutico , Animais , Antidiarreicos/isolamento & purificação , Óleo de Rícino/toxicidade , Diarreia/induzido quimicamente , Diarreia/fisiopatologia , Feminino , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Gomas Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico , Ratos , Ratos WistarRESUMO
Toxocara spp. infection and the seroconversion rate in the Amazon have been poorly investigated. This study analyzed individual and household-level risk factors for the presence of IgG antibodies to Toxocara spp. in urban Amazonian children over a period of 7 years and evaluated the seroconversion rates over a 1-year follow-up. In children < 59 months of age, the overall prevalence rate was 28.08% in 2003 and 23.35% in 2010. The 2010-2011 seroconversion rates were 13.90% for children 6-59 months of age and 12.30% for children 84-143 months of age. Multilevel logistic regression analysis identified child age, previous wheezing, and current infection with hookworm as significant associated factors for Toxocara spp. seropositivity in 2003. In 2010, age, previous helminthiasis, and having a dog were associated with seropositivity, whereas having piped water inside the household was a protective factor. Control programs mainly need to target at-risk children, water quality control, and animal deworming strategies.
Assuntos
Anticorpos Anti-Helmínticos/imunologia , Fezes/parasitologia , Imunoglobulina G/imunologia , Toxocara canis/imunologia , Toxocaríase/epidemiologia , Animais , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Carga Parasitária , Prevalência , Toxocaríase/prevenção & controle , População Urbana/estatística & dados numéricosRESUMO
BACKGROUND: The aim of this study was to analyse the prevalence of undernutrition, overweight and associated factors, before and after the implementation of the Interoceanic Highway. METHODS: A population-based cross-sectional study on children under 5 years of age was conducted in the municipality of Assis Brasil, AC, Brazil, in 2003 and 2010. Prevalence of undernutrition was observed by using height-for-age Z-scores (HAZ) and adopting a cut-off point equal to or lower than a -2 Z-score. Overweight prevalence was defined by a cut-off point equal to or greater than a +2 Z-score of the WHZ index. Z-scores were calculated relative to WHO 2006 reference data. Semi-structured questionnaires were applied to the children's guardians, investigating family socio-economic and demographic characteristics, morbidities, access to services and child care. Associated factors were identified by hierarchical multiple logistic regression analysis. RESULTS: The prevalence of low HAZ (undernutrition) was 7.0% in 2003 and 12.2% in 2010. The prevalence of high WHZ (overweight) was 1.0% and 6.6% for 2003 and 2010, respectively. It was not possible to adjust the multiple model for the year 2003. The factors associated with low HAZ in 2010 were: wealth index, the situation of living with biological parents, maternal height and presence of open sewage, whereas the factors associated with a high WHZ in the same year were: child's age, mother's time of residence in the location, mother's body mass index. CONCLUSIONS: Overweight increase within this undernutrition scenario reveals that the process of nutritional transition began in this Amazonian city only in the last decade, and therefore, it is delayed when compared to overweight in other parts of Brazil. Such nutritional transition in Assis Brasil may have been facilitated by the construction of the Interoceanic Highway.