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1.
Biochem Pharmacol ; 186: 114500, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33684388

RESUMO

The angiotensin (Ang) II converting enzyme (ACE II) pathway has recently been shown to be associated with several beneficial effects on the body, especially on the cardiac system and gastrointestinal tract. ACE II is responsible for converting Ang II into the active peptide Ang-(1-7), which in turn binds to a metabotropic receptor, the Mas receptor (MasR). Recent studies have demonstrated that Diminazene Aceturate (DIZE), a trypanosomicide used in animals, activates the ACE II pathway. In this study, we aimed to evaluate the antidiarrheal effects promoted by the administration of DIZE to activate the ACE II/Ang-(1-7)/MasR axis in induced diarrhea mice models. The results show that activation of the ACE II pathway exerts antidiarrheal effects that reduce total diarrheal stools and enteropooling. In addition, it increases Na+/K+-ATPase activity and reduces gastrointestinal transit and thus inhibits contractions of intestinal smooth muscle; decreases transepithelial electrical resistance, epithelial permeability, PGE2-induced diarrhea, and proinflammatory cytokines; and increases anti-inflammatory cytokines. Enzyme-linked immunosorbent assay (ELISA) demonstrated that DIZE, when activating the ACE II/Ang-(1-7)/MasR axis, can still interact with GM1 receptors, which reduces cholera toxin-induced diarrhea. Therefore, activation of the ACE II/Ang-(1-7)/MasR axis can be an important pharmacological target for the treatment of diarrheal diseases.


Assuntos
Angiotensina II/metabolismo , Angiotensina I/metabolismo , Antidiarreicos/uso terapêutico , Diarreia/metabolismo , Diminazena/análogos & derivados , Fragmentos de Peptídeos/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Antidiarreicos/farmacologia , Óleo de Rícino/toxicidade , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diminazena/farmacologia , Diminazena/uso terapêutico , Relação Dose-Resposta a Droga , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Masculino , Camundongos , Proto-Oncogene Mas , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia
2.
Sci Rep ; 10(1): 2696, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060388

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/metabolismo
3.
Pharmaceuticals (Basel) ; 13(1)2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31963683

RESUMO

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.

4.
Drug Dev Res ; 80(5): 666-679, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31112325

RESUMO

Inflammation is the response of the body to noxious stimuli such as infections, trauma, or injury. Experimental studies have shown that vanillic acid has anti-inflammatory effects. The objective of this study was to investigate the anti-inflammatory and antipyretic properties of the derivative of vanillic acid, isopropyl vanillate (ISP-VT), in mice. The results of this study indicated that ISP-VT reduced paw edema induced by carrageenan, dextran sulfate (DEX), compound 48/80, serotonin, bradykinin (BK), histamine (HIST), and prostaglandin E2 (PGE2). Furthermore, ISP-VT reduced recruitment of leukocytes and neutrophils and reduced its adhesion and rolling, and decreased myeloperoxidase enzyme activity (MPO), cytokine levels (tumor necrosis factor-α and interleukin-6), and vascular permeability. ISP-VT also significantly reduced the expression of cyclooxygenase-2 (COX-2) in subplantar tissue of mice. ISP-VT inhibited COX-2 selectively compared to the standard drug. Our results showed that although ISP-VT binds to COX-1, it is less toxic than indomethacin, as evidenced by MPO analysis of gastric tissue. Treatment with the ISP-VT significantly reduced rectal temperature in yeast-induced hyperthermia in mice. Our results showed that the main mechanism ISP-VT-induced anti-inflammatory activity is by inhibition of COX-2. In conclusion, our results indicate that ISP-VT has potential as an anti-inflammatory and antipyretic therapeutic compound.


Assuntos
Anti-Inflamatórios/administração & dosagem , Carragenina/efeitos adversos , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inflamação/tratamento farmacológico , Fenóis/efeitos adversos , Ácido Vanílico/química , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anticorpos Monoclonais/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Modelos Animais de Doenças , Feminino , Inflamação/induzido quimicamente , Inflamação/metabolismo , Injeções Intraperitoneais , Masculino , Camundongos , Modelos Moleculares , Fenóis/síntese química , Fenóis/química , Fenóis/farmacologia , Bibliotecas de Moléculas Pequenas/administração & dosagem , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia
5.
Nutrients ; 11(1)2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30669695

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 CFU•g body wt-1•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/farmacologia
6.
Nitric Oxide ; 78: 60-71, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29857061

RESUMO

Activation of 5' adenosine monophosphate-activated protein kinase (AMPK) stimulates production of the gaseous mediators nitric oxide (NO) and carbon monoxide (CO), which are involved in mucosal defense and gastroprotection. As AMPK itself has gastroprotective effects against several gastric ulcer etiologies, in the present study, we aimed to elucidate whether AMPK may also prevent ethanol-induced injury and play a key role in the associated gastroprotection mediated by hydrogen sulfide (H2S), NO, and CO. Mice were pretreated with AICAR (20 mg/kg, an AMPK activator) alone or with 50% ethanol. Other groups were pretreated with respective gaseous mediator inhibitors PAG, l-NAME, or ZnPP IX 30 min prior to AICAR, or with gaseous mediator donors NaHS, Lawesson's reagent and l-cysteine (H2S), SNP, l-Arginine (NO), Hemin, or CORM-2 (CO) 30 min prior to ethanol with or without compound C (10 mg/kg, a non-selective AMPK inhibitor). H2S, nitrate/nitrite (NO3-/NO2-), bilirubin levels, GSH and MDA concentration were evaluated in the gastric mucosa. The gastric mucosa was also collected for histopathological analysis and AMPK expression assessment by immunohistochemistry. Pretreatment with AICAR attenuated the ethanol-induced injury and increased H2S and bilirubin levels but not NO3-/NO2- levels in the gastric mucosa. In addition, inhibition of H2S, NO, or CO synthesis exacerbated the ethanol-induced gastric damage and inhibited the gastroprotection by AICAR. Pretreatment with compound C reversed the gastroprotective effect of NaHS, Lawesson's reagent, l-cysteine, SNP, l-Arginine, CORM-2, or Hemin. Compound C also reversed the effect of NaHS on H2S production, SNP on NO3-/NO2- levels, and Hemin on bilirubin levels. Immunohistochemistry revealed that AMPK is present at basal levels mainly in the gastric mucosa cells, and was increased by pretreatment with NaHS, SNP, and CORM-2. In conclusion, our findings indicate that AMPK activation exerts gastroprotection against ethanol-induced gastric damage and mutually interacts with H2S, NO, or CO to facilitate this process.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Monóxido de Carbono/metabolismo , Gasotransmissores/metabolismo , Sulfeto de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Gastropatias/prevenção & controle , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Animais , Bilirrubina/metabolismo , Ativação Enzimática , Ativadores de Enzimas/farmacologia , Etanol , Feminino , Mucosa Gástrica/patologia , Masculino , Camundongos , Ribonucleotídeos/farmacologia , Gastropatias/induzido quimicamente
7.
Nitric Oxide ; 76: 152-163, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28943473

RESUMO

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 , Camundongos
8.
J Clin Periodontol ; 44(6): 568-576, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28419499

RESUMO

OBJECTIVE: The aim of this study was to investigate whether experimental periodontitis cause changes to the renal tissues and imbalance in oxidative stress in kidneys. METHODS: Twenty-two female Wistar rats were separated into two groups: control and periodontitis. We assessed the following parameters: gingival bleeding index (GBI), tooth mobility, gum malondialdehyde (MDA), myeloperoxidase (MPO) activity, probing pocket depth (PPD), alveolar bone loss (ABL) for periodontal tissues; histomorphometric measures associated with renal corpuscle and histopathological aspects (evaluation of brush border) for kidneys; as also blood and urine biomarkers. Finally, we evaluated renal oxidative stress through glutathione (GSH) and MDA respectively. RESULTS: With regard to renal histomorphometry, significant differences were observed in all parameters assessed. In relation periodic acid Schiff (PAS) staining, disruption was observed of brush border in the periodontitis group in the renal tubules in comparison with the control group. The periodontitis group presented significantly higher MDA and lower GSH concentrations in the kidneys compared with animals without periodontitis. CONCLUSION: The induced periodontitis caused histomorphometric changes in renal tissues as well as disruption of the brush border in renal tubules, alterations associated with increase in oxidative stress in kidneys. However, these alterations were not sufficient to cause differences in the renal function markers.


Assuntos
Nefropatias/etiologia , Peroxidação de Lipídeos/fisiologia , Estresse Oxidativo/fisiologia , Periodontite/complicações , Periodontite/metabolismo , Perda do Osso Alveolar , Animais , Biomarcadores/sangue , Biomarcadores/urina , Modelos Animais de Doenças , Feminino , Glutationa/análise , Nefropatias/patologia , Malondialdeído/análise , Perda da Inserção Periodontal , Índice Periodontal , Bolsa Periodontal , Periodonto , Peroxidase/metabolismo , Ratos , Ratos Wistar , Mobilidade Dentária
9.
Int J Biol Macromol ; 97: 34-45, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28064049

RESUMO

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 terapêutico
10.
ACS Omega ; 2(12): 9080-9094, 2017 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-30023600

RESUMO

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.

11.
Chem Biol Interact ; 260: 129-140, 2016 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-27838229

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/agonistas
12.
Basic Clin Pharmacol Toxicol ; 118(6): 440-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26582552

RESUMO

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/metabolismo
13.
Dig Dis Sci ; 61(2): 400-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26403426

RESUMO

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/metabolismo
14.
J Ethnopharmacol ; 174: 299-307, 2015 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-26297843

RESUMO

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 Wistar
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