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1.
Nutr Res ; 125: 1-15, 2024 May.
Article in English | MEDLINE | ID: mdl-38428258

ABSTRACT

Açaí seed extract (ASE) is obtained from Euterpe oleracea Mart. (açaí) plant (Amazon region) has high nutritional and functional value. ASE is rich in polyphenolic compounds, mainly proanthocyanidins. Proanthocyanidins can modulate the immune system and oxidative stress by inhibiting the toll-like receptor-4 (TLR-4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-κB (NF-κB) pathway. A great deal of evidence suggests that inflammatory cytokines and oxidative stress contribute to the pathogenesis of intestinal mucositis, and these events can lead to intestinal dysmotility. We hypothesized that ASE acts as an anti-inflammatory and antioxidant compound in intestinal mucositis induced by 5-fluorouracil (5-FU) through modulation of the TLR-4/MyD88/phosphatidylinositol-3-kinase α/mechanistic target of rapamycin/NF-κBp65 pathway. The animals were divided into linear 5-FU (450 mg/kg) and 5-FU + ASE (10, 30, and 100 mg/kg) groups. The weight loss of the animals was evaluated daily. Samples from duodenum, jejunum, and ileum were obtained for histopathological, biochemical, and functional analyses. ASE reduced weight loss, inflammatory parameters (interleukin-1ß; tumor necrosis factor-α; myeloperoxidase activity) and the gene expression of mediators involved in the TLR-2/MyD88/NF-κB pathway. ASE prevented histopathological changes with beneficial effects on gastrointestinal transit delay, gastric emptying, and intestinal absorption/permeability. In conclusion, ASE protects the integrity of the intestinal epithelial barrier by inhibiting the TLR/MyD88/PI3K/mechanistic target of rapamycin/NF-κBp65 pathway.


Subject(s)
Euterpe , Fluorouracil , Mucositis , Myeloid Differentiation Factor 88 , Plant Extracts , Polyphenols , Seeds , Signal Transduction , TOR Serine-Threonine Kinases , Toll-Like Receptor 4 , Animals , Toll-Like Receptor 4/metabolism , Mucositis/chemically induced , Mucositis/drug therapy , Mucositis/prevention & control , Mucositis/metabolism , Myeloid Differentiation Factor 88/metabolism , TOR Serine-Threonine Kinases/metabolism , Signal Transduction/drug effects , Plant Extracts/pharmacology , Seeds/chemistry , Polyphenols/pharmacology , Male , Euterpe/chemistry , Mice , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Transcription Factor RelA/metabolism , Antioxidants/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Oxidative Stress/drug effects , Anti-Inflammatory Agents/pharmacology , NF-kappa B/metabolism
2.
J Pharm Pharmacol ; 76(6): 732-742, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38546507

ABSTRACT

OBJECTIVES: Angico gum (AG) (Anadenanthera colubrina var. Cebil [Griseb.] Altschul) is utilized by some Brazilian communities to alleviate symptoms from gastroesophageal reflux disease. Here, we aimed to investigate the "in vitro" topical protective capacity of AG on human esophageal mucosa. METHODS: Biopsies of the distal esophageal mucosa were collected from 35 patients with heartburn (24 non-erosive and 11 with erosive oesophagitis (EE)) and mounted in Üssing chambers. AG was applied topically, followed by exposure with acid solution (pH 2.0 or pH 1.0), where transepithelial electrical resistance (TER) and The transepithelial permeability for fluorescein was assessed. The incubation of the AG labeled with FITC in the esophageal mucosa was localized by fluorescence microscopy. KEY FINDINGS: Pretreatment with AG prevented the drop in TER induced by acid solution, as well as significantly decreases the fluorescein permeability in non-erosive patients. The protective effect of AG was sustained for up to 120 min both in biopsies of non-erosive and erosive esophagitis. Confocal microscope images showed mucosal luminal adherence of FITC-labeled AG. CONCLUSION: AG had a prolonged topical protective effect against acid solution in mucosal biopsies of patients with non-erosive and erosive esophagitis.


Subject(s)
Esophageal Mucosa , Gastroesophageal Reflux , Humans , Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/prevention & control , Esophageal Mucosa/drug effects , Esophageal Mucosa/pathology , Esophageal Mucosa/metabolism , Male , Female , Middle Aged , Adult , Permeability , Electric Impedance , Administration, Topical , Biopolymers , Aged , Fluorescein/administration & dosage , Esophagus/drug effects , Esophagus/pathology , Esophagus/metabolism , Heartburn/drug therapy , Heartburn/prevention & control , Clinical Relevance
3.
Laryngoscope ; 134(7): 3080-3085, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38214310

ABSTRACT

OBJECTIVE: This study aimed to evaluate the role of pepsin inhibitors in the inflammatory response and their effects on laryngeal mucosal integrity during gastroesophageal reflux (GERD) under in vivo conditions. METHODS: A surgical model of GERD was used, in which mice were treated with pepstatin (0.3 mg/kg) or darunavir (8.6 mg/kg) for 3 days. On the third day after the experimental protocol, the laryngeal samples were collected to assess the severity of inflammation (wet weight and myeloperoxidase activity) and mucosal integrity (transepithelial electrical resistance and paracellular epithelial permeability to fluorescein). RESULTS: The surgical GERD model was reproduced. It showed features of inflammation and loss of barrier function in the laryngeal mucosa. Pepstatin and darunavir administration suppressed laryngeal inflammation and preserved laryngeal mucosal integrity. CONCLUSION: Pepsin inhibition by the administration of pepstatin and darunavir improved inflammation and protected the laryngeal mucosa in a mouse experimental model of GERD. LEVEL OF EVIDENCE: NA Laryngoscope, 134:3080-3085, 2024.


Subject(s)
Disease Models, Animal , Gastroesophageal Reflux , Pepsin A , Animals , Mice , Gastroesophageal Reflux/drug therapy , Pepstatins/pharmacology , Laryngeal Mucosa/drug effects , Laryngeal Mucosa/pathology , Male , Inflammation/drug therapy , Inflammation/prevention & control
4.
Laryngoscope ; 133(1): 162-168, 2023 01.
Article in English | MEDLINE | ID: mdl-35258096

ABSTRACT

OBJECTIVE: This study aimed to evaluate the in vivo protective effect of the angico gum biopolymer in reducing the inflammatory response and preserving the integrity of the laryngeal and esophageal mucosa. STUDY DESIGN: Animal study. METHODS: A murine surgical model of gastroesophageal reflux disease was accomplished and subsequently treated with angico gum or omeprazole. On days 3 and 7 post surgery, samples of the larynx and esophagus, respectively, were collected to measure the level of inflammation (wet weight and myeloperoxidase activity) and mucosal integrity (transepithelial electrical resistance and mucosal permeability to fluorescein). RESULTS: Angico gum and omeprazole decreased laryngeal inflammation (wet weight and myeloperoxidase activity) and dramatically improved the integrity of the laryngeal mucosa. It also reduced inflammation (decreased wet weight and myeloperoxidase activity) of the esophagus and preserved the barrier function (inferred by assessing the integrity of the mucosa). CONCLUSION: This study demonstrates the protective effect of angico gum in an experimental gastroesophageal reflux disease model. Angico gum attenuates inflammation and impairment of the mucosal barrier function not only in the larynx but also in the esophagus. LEVEL OF EVIDENCE: NA Laryngoscope, 133:162-168, 2023.


Subject(s)
Esophageal Mucosa , Gastroesophageal Reflux , Mice , Animals , Gastroesophageal Reflux/drug therapy , Electric Impedance , Mucous Membrane , Disease Models, Animal
5.
Cancer Invest ; 40(8): 680-692, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35731734

ABSTRACT

We investigated the differences in prognosis according to the type of healthcare coverage of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). This study included 875 medical records. Patients covered by the publicly funded Unified Health System (SUS) had a low educational level, with advanced T stage and delayed treatment initiation. Multivariate analyses revealed an association between T stage (p = .035) and poor prognosis in oral squamous cell carcinoma, and age (p = .029) in oropharyngeal squamous cell carcinoma. Surgical treatment (p = .036) and marital status (p = .015) were considered predictors of better prognosis in OOSCC. Exclusive SUS-dependency can be considered an indirect prognostic factor for OOSCC.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Oropharyngeal Neoplasms , Brazil/epidemiology , Carcinoma, Squamous Cell/pathology , Delivery of Health Care , Humans , Mouth Neoplasms/pathology , Oropharyngeal Neoplasms/therapy , Prognosis , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/therapy
6.
Biochem Pharmacol ; 186: 114500, 2021 04.
Article in English | MEDLINE | ID: mdl-33684388

ABSTRACT

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.


Subject(s)
Angiotensin II/metabolism , Angiotensin I/metabolism , Antidiarrheals/therapeutic use , Diarrhea/metabolism , Diminazene/analogs & derivatives , Peptide Fragments/metabolism , Proto-Oncogene Proteins/metabolism , Receptors, G-Protein-Coupled/metabolism , Animals , Antidiarrheals/pharmacology , Castor Oil/toxicity , Diarrhea/chemically induced , Diarrhea/drug therapy , Diminazene/pharmacology , Diminazene/therapeutic use , Dose-Response Relationship, Drug , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/metabolism , Male , Mice , Proto-Oncogene Mas , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/physiology
7.
Laryngoscope ; 130(12): E889-E895, 2020 12.
Article in English | MEDLINE | ID: mdl-32159864

ABSTRACT

OBJECTIVES/HYPOTHESIS: The objectives of this study were to evaluate laryngeal inflammation and mucosal integrity in a murine model of reflux disease and to assess the protective effects of topical agents including alginate, hyaluronic acid, and cashew gum. STUDY DESIGN: Animal study. METHODS: A surgical murine model of reflux disease was evaluated at 3 or 7 days postsurgery, and laryngeal samples were collected to measure inflammation (wet weight and myeloperoxidase [MPO]) and mucosal integrity (transepithelial resistance [TER] and mucosal permeability to fluorescein). Additional groups of animals were administered one of several topical agents (alginate, hyaluronic acid, or cashew gum) daily, and laryngeal inflammation and mucosal integrity were evaluated at 3 days postsurgery. RESULTS: At 3 days, and not 7 days postsurgery, we observed increased laryngeal wet weight and MPO, decreased laryngeal TER, and increased laryngeal mucosa permeability. Alginate partially decreased laryngeal inflammation (wet weight and not MPO) and dramatically improved laryngeal mucosal integrity. Conversely, hyaluronic acid eliminated the inflammation; however, it had no effect on laryngeal mucosal integrity impairment. Cashew gum eliminated laryngeal inflammation as well as the impairment in laryngeal mucosal integrity. CONCLUSIONS: This study shows that a surgical model of reflux disease induced laryngeal inflammation and impairment in laryngeal barrier function. These observed alterations were partially attenuated by alginate and hyaluronic acid and completely reversed by cashew gum. LEVEL OF EVIDENCE: NA Laryngoscope, 2020.


Subject(s)
Alginates/administration & dosage , Gastroesophageal Reflux/complications , Hyaluronic Acid/administration & dosage , Laryngeal Mucosa/drug effects , Laryngeal Mucosa/pathology , Laryngitis/etiology , Laryngitis/prevention & control , Plant Gums/administration & dosage , Anacardium , Animals , Disease Models, Animal , Male , Mice
8.
Int J Biol Macromol ; 150: 354-361, 2020 May 01.
Article in English | MEDLINE | ID: mdl-32057860

ABSTRACT

This study aimed to evaluate the in vitro protective effect of topical treatment with a native sulfated polysaccharide of G. caudata (SP-Gc), hydrolyzed (H-SP-Gc), or desulfated (D-SP-Gc) polysaccharide of Gracilaria caudata in esophageal biopsies obtained from GERD patients. Biopsies were obtained from nonerosive reflux disease (NERD) patients and from erosive esophagitis patients. Then, the biopsies were mounted in an Ussing chamber to measure the basal transepithelial electrical resistance (TEER). The effect of mucosal exposure to an acid solution on TEER was analyzed with or without different concentrations (1, 0.3 or 1%) of SP-Gc, H-SP-Gc, or D-SP-Gc, precoated on the mucosa. Basal esophageal mucosal electrical resistance was significantly lower in erosive esophagitis than from NERD. Mucosal samples precoated with native SP-Gc (1%) significantly prevented TEER drop induced by an acidic solution in NERD, but this effect was not observed in erosive esophagitis. Topical application of D-SP-Gc showed no difference compared to native SP-Gc. However, when treated with chemically-modified SP-Gc, the protective effect observed with native SP-Gc was lost. The present study indicated that SP-Gc protects the human esophageal mucosal barrier in NERD patients. This effect is dependent on the structure but is independent of the presence of sulfate.


Subject(s)
Biological Products/chemistry , Biological Products/pharmacology , Gracilaria/chemistry , Mucous Membrane/drug effects , Polysaccharides/chemistry , Polysaccharides/pharmacology , Protective Agents/chemistry , Protective Agents/pharmacology , Adult , Aged , Biopsy , Esophagus , Female , Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/etiology , Gastroesophageal Reflux/metabolism , Gastroesophageal Reflux/pathology , Humans , Hydrolysis , Male , Middle Aged , Spectrum Analysis , Young Adult
9.
Carbohydr Polym ; 226: 115205, 2019 Dec 15.
Article in English | MEDLINE | ID: mdl-31582062

ABSTRACT

This study aimed to investigate a standardized biopolymer, cashew gum (CG), in human oesophageal mucosa and mice with experimentally-induced non-erosive reflux disease (NERD). Human oesophageal biopsies from NERD patients were collected to evaluate the mucosal protection of CG through transepithelial electrical resistance (TER), mucosal permeability, and mucoadhesiveness tests. A surgical model of NERD in mice was induced, and barrier functions followed by suggestive oesophageal inflammatory hallmarks were evaluated. Pre-coating of CG was effective in human oesophageal mucosa by attenuating drop of TER and mucosal permeability. Labelled-CG adheres to human oesophageal mucosa for up to 1 h. In animal studies, CG improved parameters of barrier function (TER and mucosal permeability) in distal oesophagus mucosa. CG also promoted sequential support by reducing inflammatory hallmarks of oesophageal damage. CG confers topical oesophageal mucosal protection due to its mucoadhesiveness and anti-inflammatory profile. Long-duration mucoprotective products can be further explored as first-line/adjuvant NERD therapy.


Subject(s)
Anacardium/metabolism , Biopolymers/pharmacology , Biopolymers/pharmacokinetics , Esophageal Mucosa , Gastroesophageal Reflux/drug therapy , Adult , Aged , Animals , Electric Impedance , Esophageal Mucosa/drug effects , Esophageal Mucosa/metabolism , Female , Humans , Mice , Middle Aged , Permeability/drug effects , Protective Agents/pharmacology , Young Adult
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