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1.
Inflammopharmacology ; 32(5): 3389-3398, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39126571

RESUMO

Syagrus coronata, a native palm tree in the Caatinga domain, produces fixed oil (ScFO) used therapeutically and dietary by Northeast Brazilian communities. This study evaluated its anti-inflammatory potential of CFA-induced arthritis and its effect on behavioral parameters. In the acute model, ScFO at 25, 50, and 100 mg/kg showed edematogenic effects similar to indomethacin at 4 mg/kg (p > 0.05). In the arthritis model, 100 mg/kg ScFO treatment was comparable to indomethacin (4 mg/kg) (p > 0.05). TNF-α and IL-1ß levels were significantly reduced in ScFO-treated groups at 25, 50, and 100 mg/kg, and the indomethacin group (4 mg/kg) versus the positive control (p > 0.05). Radiographs showed severe soft-tissue swelling and bone deformities in the control group, while the 100 mg/kg ScFO group had few alterations, similar to the indomethacin group. Histopathological analysis revealed intense lymphocytic infiltration in the control group, mild diffuse lymphocytic infiltration in the indomethacin group, and mild lymphoplasmacytic infiltration with focal polymorphonuclear infiltrates in the 100 mg/kg ScFO group. Behavioral analysis showed improved exploratory stimuli in ScFO and indomethacin-treated mice compared to the positive control (p > 0.05). ScFO demonstrated anti-inflammatory effects in both acute and chronic arthritis models, reducing edema and pro-inflammatory cytokines, and improved exploratory behavior due to its analgesic properties.


Assuntos
Anti-Inflamatórios , Artrite Experimental , Adjuvante de Freund , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Camundongos , Anti-Inflamatórios/farmacologia , Masculino , Óleos de Plantas/farmacologia , Arecaceae/química , Edema/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-1beta/metabolismo , Óleo de Palmeira/farmacologia , Indometacina/farmacologia , Brasil , Relação Dose-Resposta a Droga
2.
Molecules ; 29(14)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39064929

RESUMO

Indomethacin (INDO) has a mechanism of action based on inhibiting fatty acids cyclooxygenase activity within the inflammation process. The action mechanism could be correlated with possible anticancer activity, but its high toxicity in normal tissues has made therapy difficult. By the coprecipitation method, the drug carried in a layered double hydroxides (LDH) hybrid matrix would reduce its undesired effects by promoting chemotherapeutic redirection. Therefore, different samples containing INDO intercalated in LDH were synthesized at temperatures of 50, 70, and 90 °C and synthesis times of 8, 16, 24, and 48 h, seeking the best structural organization. X-ray diffraction (XRD), vibrational Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), spectrophotometric analysis in UV-VIS, and differential thermogravimetric analysis (TGA/DTA) were used for characterization. Our results indicate that higher temperatures and longer synthesis time through coprecipitation reduce the possibility of INDO intercalation. However, it was possible to establish a time of 16 h and a temperature of 50 °C as the best conditions for intercalation. In vitro results confirmed the cell viability potential and anticancer activity in the LDH-INDO sample (16 h and 50 °C) for gastric cancer (AGP01, ACP02, and ACP03), breast cancer (MDA-MB-231 and MCF-7), melanoma (SK-MEL-19), lung fibroblast (MRC-5), and non-neoplastic gastric tissue (MN01) by MTT assay. Cell proliferation was inhibited, demonstrating higher and lower toxicity against MDA-MB-231 and SK-MEL-19. Thus, a clinical redirection of INDO is suggested as an integral and adjunctive anticancer medication in chemotherapy treatment.


Assuntos
Antineoplásicos , Hidróxidos , Indometacina , Nanopartículas , Humanos , Nanopartículas/química , Indometacina/farmacologia , Indometacina/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Hidróxidos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Proliferação de Células/efeitos dos fármacos
3.
Int J Biol Macromol ; 270(Pt 1): 132062, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38705340

RESUMO

Oral drug administration, especially when composed of mucoadhesive delivery systems, has been a research trend due to increased residence time and contact with the mucosa, potentially increasing drug bioavailability and stability. In this context, this study aimed to develop self-assembly mucoadhesive beads composed of blends of κ-carrageenan and sericin (κ-Car/Ser) loaded with the anti-inflammatory drug indomethacin (IND). We investigated the swelling, adhesion behaviour, and mechanical/physical properties of the beads, assessing their effects on cell viability, safety and permeation characteristics in both 2D and triple-culture model. The swelling ratio of the beads indicated pH-responsiveness, with maximum water absorption at pH 6.8, and strong mucoadhesion, increasing primarily with higher polymer concentrations. The beads exhibited thermal stability and no chemical interaction with IND, showing improved mechanical properties. Furthermore, the beads remained stable during accelerated and long-term storage studies. The beads were found to be biocompatible, and IND encapsulation improved cell viability (>70 % in both models, 79 % in VN) and modified IND permeation through the models (6.3 % for F5 formulation (κ-Car 0.90 % w/v | Ser 1.2 % w/v| IND 3.0 g); 10.9 % for free IND, p < 0.05). Accordingly, κ-Car/Ser/IND beads were demonstrated to be a promising IND drug carrier to improve oral administration while mitigating the side effects of non-steroidal anti-inflammatories.


Assuntos
Carragenina , Preparações de Ação Retardada , Indometacina , Sericinas , Indometacina/química , Indometacina/administração & dosagem , Indometacina/farmacocinética , Carragenina/química , Administração Oral , Humanos , Sericinas/química , Preparações de Ação Retardada/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Sobrevivência Celular/efeitos dos fármacos , Microesferas , Animais , Células CACO-2 , Concentração de Íons de Hidrogênio
4.
Nutrients ; 16(10)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38794668

RESUMO

INTRODUCTION: Justicia pectoralis Jacq. is traditionally applied in folk medicine in Brazil and in several Latin American countries. The leaves are used in tea form, especially in the treatment of respiratory disorders, acting as an expectorant. It also has activity in gastrointestinal disorders, and it is anti-inflammatory, antioxidant, sedative, and estrogenic, among others. AIMS: To investigate the gastroprotective activity of the methanol extract of the leaves of Justicia pectoralis Jacq. (MEJP) in different experimental models of gastric ulcers. MATERIALS AND METHODS: The adult leaves of Justicia pectoralis Jacq. were collected and cultivated in beds, with an approximate spacing of 40 × 40 cm, organic fertilization, irrigation with potable water and without shelter from light. The MEJP was prepared from the dried and pulverized leaves and concentrated under reduced pressure in a rotary evaporator. For the experimental model of gastric ulcer, Swiss male albino mice were used. The inputs used in the experiment were MEJP at three different concentrations (250, 500 and 1000 mg/kg p.o.), cimetidine (50 mg/kg p.o.), indomethacin (50 mg/kg s.c.) and vehicle (10 mL/kg p.o.). RESULTS: MEJP (250, 500 and 1000 mg/kg p.o.) demonstrated gastroprotective activity, with levels of protection of 45.65%, 44.80% and 40.22%, respectively, compared to the control (vehicle). Compared with cimetidine (48.29%), MEJP showed similar gastroprotective activity. CONCLUSIONS: This study demonstrated the gastroprotective activity of MEJP and contributes to validate the traditional use the species for gastric disorders and provides a pharmacological basis for its clinical potential.


Assuntos
Extratos Vegetais , Folhas de Planta , Úlcera Gástrica , Animais , Extratos Vegetais/farmacologia , Camundongos , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Folhas de Planta/química , Masculino , Antiulcerosos/farmacologia , Metanol/química , Justicia/química , Modelos Animais de Doenças , Cimetidina/farmacologia , Acanthaceae/química , Indometacina , Brasil , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia
5.
PeerJ ; 12: e17062, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435992

RESUMO

Background: Obesity leads to an elevated risk of developing gastrointestinal disease such as gastric ulcers. Callistemon citrinus leaf extract has shown antioxidant, antimicrobial, hepatoprotective, and chemoprotective effects against colon cancer. The aim of this study is to evaluate the gastroprotective effect of C. citrinus leaf extract on indomethacin-induced gastric ulcers in obese rats. Methods: Gastric ulcers were induced in female obese Wistar rats using a single oral dose of indomethacin (IND). In the first stage, the rats were fed with a high fat sugar diet (HFSD) for 15 weeks to induce obesity and, at the same time, the diet of the other group of animals included daily administration of ethanolic C. citrinus leaf extract (250 mg/kg) in addition to HFSD. In the second stage, gastric ulcers were induced with IND (30 mg/kg). The gastroprotective activity of C. citrinus, the inflammatory enzyme activities, and cytokines in the stomach were determined. Results: C. citrinus produced a reduction of gastric lesions caused by IND. Myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX) activities also decreased. Although inflammatory biomarkers such as TNFα, IL-6, AOPP, and leptin were significantly decreased by C. citrinus, adiponectin levels increased. Moreover, C. citrinus decreased weight gain and morphological and biochemical parameters. Conclusion: The use of indomethacin in rats fed with a high fat-sugar diet increased gastric ulcers. Gastroprotective effect of C. citrinus in obese rats is attributed to the reduction of pro-inflammatory cytokines and the inflammatory enzymes.


Assuntos
Indometacina , Úlcera Gástrica , Feminino , Ratos , Animais , Úlcera Gástrica/induzido quimicamente , Ratos Wistar , Anti-Inflamatórios , Obesidade/complicações , Antígenos CD36 , Açúcares , Citocinas , Extratos Vegetais/farmacologia
6.
Braz J Biol ; 83: e277354, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38452187

RESUMO

This study aimed to explore the diuretic activity of linalyl acetate (LA). LA is an essential oil, it is an integral phyto-constituent of various plants. In this study, acute and chronic diuretic activities were explored by measuring the levels of different electrolytes and pH in the urine of experimental rats. Rats were divided into five groups. The control group was given 10 mg/kg normal saline, the treated group was given 10 mg/kg furosemide, and the remaining 3 groups received different doses of LA including 25, 50, and 75 mg/kg through intraperitoneal route, to determine its diuretic potential. Urine volume for acute diuretic activity was measured for 6 hours however for chronic diuretic activity was measured for 6 days. For a comparative study of LA with a control group and treated group with reference drug, diuretic index was used. Moreover, the underlying mechanism of the diuretic activity was also explored by comparing atropine, L-NAME, and indomethacin. The results of each group with 6 rats in each group were obtained by ± standard error of the mean of every group. Analysis of Variance (ANOVA) was used for statistical analysis. Results revealed that the LA 75 mg/kg dose showed comparable results as of furosemide. Moreover, this study revealed the involvement of muscarinic receptors to produce diuresis in comparison with atropine with very little involvement of prostanoids and no effect on NO pathway induced by indomethacin and L-NAME respectively. It is concluded that LA possess anti-diuretic potential. Muscarinic receptors might be involved in producing diuretic effects.


Assuntos
Diuréticos , Furosemida , Monoterpenos , Ratos , Animais , Furosemida/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Diuréticos/farmacologia , Indometacina/farmacologia , Atropina/farmacologia , Extratos Vegetais/farmacologia , Receptores Muscarínicos
7.
Langmuir ; 40(3): 1869-1877, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38194363

RESUMO

Characterization studies of 1-butyl-3-methyl-imidazolium bis(2-ethylhexyl) sulfosuccinate vesicles at different pH values have been carried out by using liquid surface tension, transmission electron microscopy, and dynamic light scattering. The results show that there are no vesicle changes in its size and negative Z potential at pH 3, 6, and 10. Furthermore, indomethacin and 1-naphthol, both pH-dependent, electroactive, and fluorescence probes, were used to further characterize the bilayer employing electrochemical and emission techniques. The partition of indomethacin and 1-naphthol between the water and bilayer pseudophases only occurs for the neutral species and does not happen for the anionic species because the highly negative Z bilayer potential prevents incorporation due to negative repulsion. For the neutral species, the partition constant values were evaluated by square wave voltammetry and emission spectroscopy. Finally, for the indomethacin incorporated into the vesicle bilayer at pH 3, the release profile was monitored over time at pH 6. It was found that a change in the pH values causes the complete release of indomethacin after 25 min, which led us to think that the vesicles presented in this work can be used as a pH-sensitive nanocarrier for neutral pH-sensitive drugs.


Assuntos
Indometacina , Naftóis , Succinatos , Espectrometria de Fluorescência , Concentração de Íons de Hidrogênio
8.
Naunyn Schmiedebergs Arch Pharmacol ; 397(3): 1715-1725, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37721555

RESUMO

RATIONALE: Indomethacin (INDO) is a widely utilized non-steroidal anti-inflammatory drug (NSAID) with recognized effect on the central nervous system. Although previous reports demonstrate that prolonged treatment with indomethacin can lead to behavioral alterations such as anxiety disorder, the biochemical effect exerted by this drug on the brain are not fully understood. OBJECTIVES: The aim of present study was to evaluate if anxiety-like behavior elicited by indomethacin is mediated by brains oxidative stress as well as if alpha-tocopherol, a potent antioxidant, is able to prevent the behavioral and biochemical alterations induced by indomethacin treatment. METHODS: Zebrafish were utilized as experimental model and subdivided into control, INDO 1 mg/Kg, INDO 2 mg/Kg, INDO 3 g/Kg, α-TP 2 mg/Kg, α-TP 2 mg/Kg + INDO 1 mg/Kg and α-TP + INDO 2 mg/Kg groups. Vertical distributions elicited by novelty and brain oxidative stress were utilized to determinate behavioral and biochemical alterations elicited by indomethacin treatment, respectively. RESULTS: Our results showed that treatment with indomethacin 3 mg/kg induces animal death. No changes in animal survival were observed in animals treated with lower doses of indomethacin. Indomethacin induced significant anxiogenic-like behavior as well as intense oxidative stress in zebrafish brain. Treatment with alpha-tocopherol was able to prevent anxiety-like behavior and brain oxidative stress induced by indomethacin. CONCLUSIONS: Data presented in current study demonstrated for the first time that indomethacin induces anxiety-like behavior mediated by brain oxidative stress in zebrafish as well as that pre-treatment with alpha-tocopherol is able to prevent these collateral effects.


Assuntos
Indometacina , Peixe-Zebra , Animais , Indometacina/toxicidade , alfa-Tocoferol/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Estresse Oxidativo , Encéfalo , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Ansiedade/prevenção & controle
9.
FEBS J ; 291(4): 722-743, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37947039

RESUMO

Physiologically, renal medullary cells are surrounded by a hyperosmolar interstitium. However, different pathological situations can induce abrupt changes in environmental osmolality, causing cell stress. Therefore, renal cells must adapt to survive in this new condition. We previously demonstrated that, among the mechanisms involved in osmoprotection, renal cells upregulate triglyceride biosynthesis (which helps preserve glycerophospholipid synthesis and membrane homeostasis) and cyclooxygenase-2 (which generates prostaglandins from arachidonic acid) to maintain lipid metabolism in renal tissue. Herein, we evaluated whether hyperosmolality modulates phospholipase A2 (PLA2 ) activity, leading to arachidonic acid release from membrane glycerophospholipid, and investigated its possible role in hyperosmolality-induced triglyceride synthesis and accumulation. We found that hyperosmolality induced PLA2 expression and activity in Madin-Darby canine kidney cells. Cytosolic PLA2 (cPLA2) inhibition, but not secreted or calcium-independent PLA2 (sPLA2 or iPLA2 , respectively), prevented triglyceride synthesis and reduced cell survival. Inhibition of prostaglandin synthesis with indomethacin not only failed to prevent hyperosmolality-induced triglyceride synthesis but also exacerbated it. Similar results were observed with the peroxisomal proliferator activated receptor gamma (PPARγ) agonist rosiglitazone. Furthermore, hyperosmolality increased free intracellular arachidonic acid levels, which were even higher when prostaglandin synthesis was inhibited by indomethacin. Blocking PPARγ with GW-9662 prevented the effects of both indomethacin and rosiglitazone on triglyceride synthesis and even reduced hyperosmolality-induced triglyceride synthesis, suggesting that arachidonic acid may stimulate triglyceride synthesis through PPARγ activation. These results highlight the role of cPLA2 in osmoprotection, since it is essential to provide arachidonic acid, which is involved in PPARγ-regulated triglyceride synthesis, thus guaranteeing cell survival.


Assuntos
PPAR gama , Prostaglandinas , Animais , Cães , PPAR gama/genética , Ácido Araquidônico/metabolismo , Rosiglitazona , Pressão Osmótica , Fosfolipases A2 , Indometacina , Homeostase , Glicerofosfolipídeos , Triglicerídeos
10.
J Pediatr ; 266: 113877, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38135028

RESUMO

We evaluated changes in patent ductus arteriosus (PDA) diagnosis and treatment from 2012 through 2021 in a network of US academic hospitals. PDA treatment decreased among infants born at 26-28 weeks but not among infants born at 22-25 weeks. Rates of indomethacin use and PDA ligation decreased while acetaminophen use and transcatheter PDA closure increased.


Assuntos
Permeabilidade do Canal Arterial , Recém-Nascido , Lactente , Estados Unidos , Criança , Humanos , Permeabilidade do Canal Arterial/cirurgia , Recém-Nascido Prematuro , Ibuprofeno/uso terapêutico , National Institute of Child Health and Human Development (U.S.) , Indometacina/uso terapêutico
11.
J Med Food ; 26(11): 777-798, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37902784

RESUMO

The aim of this study was to systematically review the scientific literature, with Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines, of the articles found in the past 11 years on the gastroprotective role of fruit extracts in gastric ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs). Scientific articles published between 2010 and 2020 were included in this systematic review, including in vitro and in vivo models, to define the gastroprotective role of fruit extracts. Studies were selected by Rayyan using PubMed, Web of Science, Scopus, and Science Direct databases. The keywords for the search strategy were: "gastric injury," "gastric ulcer," "fruit," "indomethacin," and "aspirin." Twenty-two articles with animal models of gastric ulcers were included. The NSAIDs used were aspirin and indomethacin. To know the damage caused by these, the ulceration index and biomarkers, such as aggressive/defensive factors involved in the gastric ulceration process, were measured. Most studies have shown that fruit extracts have antiulcer activity, with the most abundant metabolites being flavonoids, followed by terpenes and alkaloids. Possible antiulcer activities such as antioxidant, cytoprotective, gastric acid antisecretory, anti-inflammatory, or angiogenesis stimulant were declared, manifested mainly as a reduction of lipid peroxidation products, an increase in antioxidant enzymes and prostaglandins, and by the formation of a protective film through protein precipitation in the ulcer area. This systematic review demonstrates the importance of fruit extracts as gastric protectors.


Assuntos
Antiulcerosos , Úlcera Gástrica , Ratos , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Antioxidantes/metabolismo , Frutas/metabolismo , Mucosa Gástrica/metabolismo , Extratos Vegetais/uso terapêutico , Ratos Wistar , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Indometacina/efeitos adversos , Aspirina/efeitos adversos , Aspirina/metabolismo
12.
Biomolecules ; 13(9)2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37759783

RESUMO

Indomethacin is a non-selective NSAID used against pain and inflammation. Although cyclooxygenase (COX) inhibition is considered indomethacin's primary action mechanism, COX-independent ways are associated with beneficial effects in cancer. In colon cancer cells, the activation of the peroxisome proliferator-activated receptor-γ (PPAR-γ) is related to the increase in spermidine/spermine-N1-acetyltransferase-1 (SSAT-1), a key enzyme for polyamine degradation, and related to cell cycle arrest. Indomethacin increases the SSAT-1 levels in lung cancer cells; however, the mechanism relying on the SSAT-1 increase is unclear. Thus, we asked for the influence of the PPAR-γ on the SSAT-1 expression in two lung cancer cell lines: H1299 and A549. We found that the inhibition of PPAR-γ with GW9662 did not revert the increase in SSAT-1 induced by indomethacin. Because the mRNA of SSAT-1 suffers a pre-translation retention step by nucleolin, a nucleolar protein, we explored the relationship between indomethacin and the upstream translation regulators of SSAT-1. We found that indomethacin decreases the nucleolin levels and the cyclin-dependent kinase 1 (CDK1) levels, which phosphorylates nucleolin in mitosis. Overexpression of nucleolin partially reverts the effect of indomethacin over cell viability and SSAT-1 levels. On the other hand, Casein Kinase, known for phosphorylating nucleolin during interphase, is not modified by indomethacin. SSAT-1 exerts its antiproliferative effect by acetylating polyamines, a process reverted by the polyamine oxidase (PAOX). Recently, methoctramine was described as the most specific inhibitor of PAOX. Thus, we asked if methoctramine could increase the effect of indomethacin. We found that, when combined, indomethacin and methoctramine have a synergistic effect against NSCLC cells in vitro. These results suggest that indomethacin increases the SSAT-1 levels by reducing the CDK1-nucleolin regulatory axis, and the PAOX inhibition with methoctramine could improve the antiproliferative effect of indomethacin.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Humanos , Acetiltransferases/genética , Proteína Quinase CDC2 , Ciclo-Oxigenase 2 , Indometacina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Oxirredutases , Receptores Ativados por Proliferador de Peroxissomo , Poliamina Oxidase , Nucleolina
13.
Eur J Pharm Biopharm ; 191: 114-123, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37652137

RESUMO

The potentiation of pharmacological effects can be achieved through several strategies, such as the association of substances and delivery in nanostructured systems. In practice, potentiation can be measured by the law of mass action and joint evaluation of the combination index (CI) and dose-response curves. In this context, this study aimed to evaluate the anti-inflammatory effect of the association of ß-caryophyllene and indomethacin in the free form and delivered in nanoemulsions using the in vitro model of LPS-stimulated murine macrophage. The results indicated potentiation of the anti-inflammatory effect of nanoemulsified substances compared to free substances, as well as synergistic action between the sesquiterpene and the selected NSAID. In comparison, the association of ß-caryophyllene and indomethacin in the free form inhibited the production of nitric oxide by 50% at 48.60 µg/mL (CI = 0.21), while the nanoemulsified association of these substances resulted in an IC50 of 1.45 µg/mL (CI = 0.14). In parallel, cytotoxicity assays on HaCaT and MRC-5 cell lines demonstrated the safety of IC50-equivalent concentrations of the anti-inflammatory action, and no irritating effects on the chorioallantoic membrane of embryonated eggs were observed (HET-CAM assay). The results suggest that ß-caryophyllene may be an alternative to replace an inert oily core in nanoemulsion systems when anti-inflammatory effects are desirable.


Assuntos
Indometacina , Lipopolissacarídeos , Camundongos , Animais , Indometacina/farmacologia , Indometacina/metabolismo , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Macrófagos
14.
An Acad Bras Cienc ; 95(suppl 1): e20220427, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37556712

RESUMO

The antiulcer mechanisms of the dry extract of T. erecta flowers (DETe) were studied here. The acute ulcers induced by acidified ethanol or indomethacin were reproduced in mice pretreated with DETe (3 - 300 mg/kg). The antiulcer activity of DETe was also verified in mice pretreated with NEM, L-NAME, indomethacin, or yohimbine. The antisecretory effect of DETe was verified in rats, and its anti-Helicobacter pylori activity was determined in vitro. DETe (300 mg/kg, p.o) reduced the ethanol- or indomethacin-induced ulcer by 49 and 93%, respectively. The pre-treatment with L-NAME, NEM or yohimbine abolished the gastroprotective effect of DETe. However, DETe did not change the volume, acidity, or peptic activity in rats and did not affect H. pylori. This study expands knowledge about the antiulcerogenic potential of DETe, evidencing the role of nitric oxide, non-protein sulfhydryl groups, α2 adrenergic receptors, and prostaglandins, but not antisecretory or anti-H. pylori properties.


Assuntos
Extratos Vegetais , Tagetes , Ratos , Camundongos , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos Wistar , NG-Nitroarginina Metil Éster/farmacologia , Mucosa Gástrica , Indometacina/farmacologia , Ioimbina/farmacologia , Etanol/farmacologia , Flores
15.
Int J Biol Macromol ; 246: 125558, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37392907

RESUMO

Modified release of multiparticulate pharmaceutical forms is a key therapeutic strategy to reduce side effects and toxicity caused by high and repeated doses of immediate-release oral drugs. This research focused on the encapsulation of indomethacin (IND) in the crosslinked k-Car/Ser polymeric matrix by covalent and thermal methods to evaluate drug delivery modulation and properties of the crosslinked blend. Therefore, the entrapment efficiency (EE %), drug loading (DL %) and physicochemical properties of the particles were investigated. The particles presented a spherical shape and a rough surface with a mean diameter of 1.38-2.15 mm (CCA) and 1.56-1.86 mm (thermal crosslink). FTIR investigation indicated the presence of IDM in the particles and X-ray pattern showed the maintenance of crystallinity of IDM. The in vitro release in acidic medium (pH 1.2) and phosphate buffer saline solution (pH 6.8) was 1.23-6.81 % and 81-100 %, respectively. Considering the results, the formulations remained stable after 6 months. The Weibull equation was adequately fitted for all formulations and a diffusion mechanism, swelling and relaxation of chain were observed. IDM-loaded k-carrageenan/sericin/CMC increases cell viability (> 75 % for neutral red and > 81 % for MTT). Finally, all formulations present gastro-resistance, pH response and altered release and have the potential to be used as drug delivery careers.


Assuntos
Indometacina , Sericinas , Indometacina/química , Carragenina , Preparações Farmacêuticas , Sistemas de Liberação de Medicamentos
16.
Int J Pharm ; 642: 123122, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37307959

RESUMO

Amorphous solid dispersions (ASDs) based on water-insoluble hydrophilic polymers can sustain supersaturation in their kinetic solubility profiles (KSPs) compared to soluble carriers. However, in the limit of very high swelling capacity, the achievable extent of drug supersaturation has not been fully examined. This study explores the limiting supersaturation behavior of ASDs of poorly soluble indomethacin (IND) and posaconazole (PCZ) based on a high-swelling excipient, low-substituted hydroxypropyl cellulose (L-HPC). Using IND as a reference, we showed that the rapid initial supersaturation buildup in the KSP of IND ASD can be simulated through sequential IND infusion steps, however at large times the KSP of IND release from ASD appears more sustained than direct IND infusion. This has been attributed to potential trapping of seed crystals generated in the L-HPC gel matrix thus limiting their growth and rate of desupersaturation. Similar result is also expected in PCZ ASD. Furthermore, the current drug loading process for ASD preparation resulted in the agglomeration of L-HPC based ASD particles, producing granules of up to 300-500 µm (cf. 20 µm individual particle), with distinct kinetic solubility profiles. This feature makes L-HPC particularly suitable as ASD carriers for fine tuning of supersaturation to achieve enhanced bioavailability for poorly soluble drugs.


Assuntos
Celulose , Indometacina , Preparações Farmacêuticas , Cristalização/métodos , Celulose/química , Solubilidade , Indometacina/química , Liberação Controlada de Fármacos
18.
J Pediatr ; 259: 113457, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37172814

RESUMO

OBJECTIVE: To estimate if the odds of spontaneous intestinal perforation (SIP) are increased when antenatal steroids (ANS) given close to delivery are combined with indomethacin on day 1 after birth (Indo-D1). STUDY DESIGN: A retrospective cohort study using the Neonatal Research Network (NRN) database of inborn infants, gestational age 220-286 weeks or birth weight of 401-1000 g, born between January 1, 2016 and December 31, 2019, and surviving >12 hours. The primary outcome was SIP through 14 days. Time of last ANS dose prior to delivery was analyzed as a continuous variable (using 169 hours for durations >168 hours or no steroid exposure). Associations between ANS, Indo-D1, and SIP were obtained from a multilevel hierarchical generalized linear mixed model after covariate adjustment. This yielded aOR and 95% CI. RESULTS: Of 6851 infants, 243 had SIP (3.5%). ANS exposure occurred in 6393 infants (93.3%) and IndoD1 was given to 1863 infants (27.2%). The time (median, IQR) from last dose of ANS to delivery was 32.5 hours (6-81) vs 37.1 hours (7-110) for infants with or without SIP, respectively (P = .10). Indo-D1 was given to 51.9 vs 26.3% of infants with SIP vs no SIP, respectively (P < .0001). Adjusted analysis indicated no interaction between time of last ANS dose and Indo-D1 for SIP (P = .7). Indo-D1 but not ANS was associated with increased odds of SIP (aOR: 1.73, 1.21-2.48, P = .003). CONCLUSION: The odds of SIP were increased after receipt of Indo-D1. Exposure to ANS prior to Indo-D1 was not associated with an increase in SIP.


Assuntos
Indometacina , Perfuração Intestinal , Recém-Nascido , Lactente , Humanos , Feminino , Gravidez , Adulto Jovem , Adulto , Indometacina/efeitos adversos , Estudos Retrospectivos , Idade Gestacional , Peso ao Nascer , Esteroides
19.
Braz J Med Biol Res ; 56: e12665, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37255094

RESUMO

There are few studies addressing duodenal inflammation. This study was designed to investigate the effects of a recently developed biotechnological product, a nano-formulation of olmesartan medoxomil (OM) - olmesartan medoxomil zeinmersomes (OMZ) - for the treatment of indomethacin-induced duodenitis in rats. Adult male Wistar rats were given indomethacin (10 mg/kg/day) for four weeks. They were divided into a positive control group (PC, untreated) and two groups treated orally with 3 mg/kg per day of OM or OMZ for the last two weeks of the 4-week indomethacin-treatment. At end of the four weeks, blood and duodenum were collected. Duodenal homogenate was used for measurement of levels of myeloperoxidase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde, reduced glutathione (GSH), and cleaved caspase-3. Duodenal sections were stained with H&E. Gene expressions of nuclear factor kappa B (NF-κB p65), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) by RT-PCR, and protein expression of survivin by western blot were assessed. Plasma and duodenal olmesartan concentrations were measured by high performance liquid chromatography mass spectrometry. The duodenitis rats showed significantly higher duodenal levels of myeloperoxidase, TNF-α, IL-6, malondialdehyde, and cleaved caspase-3, a significantly lower GSH level, and histopathological alterations. Moreover, they showed upregulated gene expressions of NF-κB p65 and Bax, downregulated gene expression of Bcl-2, decreased Bcl-2/Bax ratio, and lower protein expression of survivin. OMZ was more effective in protecting the duodenum from indomethacin-induced injuries compared to OM due to improved delivery, higher bioavailability, and better anti-inflammatory, antioxidant, and antiapoptotic effects. OMZ could be a better choice for hypertensive patients with non-steroidal anti-inflammatory drugs-induced duodenitis.


Assuntos
Duodenite , NF-kappa B , Ratos , Masculino , Animais , Olmesartana Medoxomila , NF-kappa B/metabolismo , Ratos Wistar , Survivina , Peroxidase , Caspase 3 , Fator de Necrose Tumoral alfa/metabolismo , Indometacina , Interleucina-6 , Proteína X Associada a bcl-2 , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Malondialdeído/metabolismo
20.
Food Funct ; 14(7): 3242-3258, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-36928439

RESUMO

Nopalea cochenillifera (Cactaceae), popularly known as "palma" or "palma doce", is from Mexico, but it was widely introduced in Brazil through crops. It has been used as food and in traditional medicine and is a good source of phenolic compounds. In this study the phytochemical profile and gastroprotective activity of phenolic-rich extract of N. cochenillifera in acute gastric lesion models induced by ethanol and indomethacin were evaluated. High-performance liquid chromatography coupled with mass spectrometry (HPLC/ESI/MSn) allowed the characterization of 12 compounds such as sugars, phenolics and flavonoids. Among polyphenols, the main peak was assigned to isorhamnetin-3-O-(2'',3''-O-di-rhamnose)-glucoside. The TPC and TFC in the dry extract were 67.85 mg of gallic acid equivalent per g/extract and 46.16 mg quercetin equivalent per g/extract, respectively. In the in vitro MTT assay, the extract showed no cytotoxicity and suppressed ROS levels in LPS-treated RAW 264.7 cells. Preclinical models in rats showed that a dose of 100 mg kg-1 (p < 0.0001) in the ethanol model and doses of 100 mg kg-1 (p < 0.5) and 200 mg kg-1 (p < 0.01) in the indomethacin model reduced the gastric lesions. Also, the extract reduced the MPO, MDA, TNF-α and IL-1ß levels and increased the GSH and IL-10 levels. The pre-treatment with the extract led to the upregulation of SOD and the downregulation of COX-2 by immunohistochemical analysis. It also showed a cytoprotective effect in the histopathological analysis and stimulated the restoration of the mucus content as observed in the periodic acid-Schiff analysis without modifying the pH, volume or total acidity of the gastric juice. Taken together, N. cochenillifera extract can be applied as a novel gastroprotective ingredient for food or pharmaceutical products.


Assuntos
Antiulcerosos , Cactaceae , Úlcera Gástrica , Ratos , Animais , Extratos Vegetais/química , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Antiulcerosos/química , Etanol/química , Indometacina/efeitos adversos , Estresse Oxidativo , Modelos Teóricos , Mucosa Gástrica/metabolismo
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