Gastrointestinal permeability during exercise: effects of aspirin and energy-containing beverages

Lambert, G. P.; Broussard, Lorenzo J.; Mason, Benjamin L.; Mauermann, William J.; Gisolfi, C. V.

doi:10.1152/jappl.2001.90.6.2075

Cited by 90 publications

(87 citation statements)

References 24 publications

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“…The observed difference between LF and placebo did not reach statistical significance because of a wide range in results. It has been shown previously applying the urinary sucrose excretion method that aspirin administration increased gastroduodenal permeation (Lambert et al, 2001), indicating that NSAIDs inflict damage to gastric and duodenal mucosa. The observed trend in the present study warrants further investigation with sufficient power in order to elucidate the extent and pathophysiology of LF-associated protection of NSAID-induced damage to the stomach and the proximal duodenum.…”

Section: Discussionmentioning

confidence: 91%

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

2003

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Objective: To determine whether recombinant human lactoferrin ingestion inhibits nonsteroidal antiinflammatory drugs (NSAID)-induced gastroenteropathy in vivo in healthy volunteers as a model for disorders associated with a rise in permeability of the stomach and the small intestine. Design: A randomized crossover dietary intervention. Subjects and interventions: In all, 15 healthy volunteers (age 2371.4 y) were tested. A sucrose and a lactulose/rhamnose (L/R) permeability test was performed to assess gastroduodenal and small intestine permeability as indicator of NSAID-induced gastroenteropathy. All subjects consumed standardized meals for 2 days. On the second day at time ¼ À24 h each subject ingested a drink containing 5 g recombinant human lactoferrin or placebo during breakfast. At t ¼ À9 h, subjects ingested the same drink with 75 mg of the NSAID indomethacin and after an overnight fast at t ¼ À1 h subjects consumed the drink and 50 mg indomethacin. After 1 h, at t ¼ 0, a permeability test was performed. Results: Small intestine permeability after indomethacin and placebo was significantly higher (L/R ratio ¼ 0.036; 0.014-0.092, Po0.05) compared to the permeability observed after ingestion of indomethacin and lactoferrin (0.028; 0.015-0.056), whereas gastroduodenal permeability did not differ between the two interventions (P ¼ 0.3). Conclusion: Oral recombinant human lactoferrin supplementation during a short-term indomethacin challenge reduced the NSAID-mediated increase in small intestinal permeability and hence may provide a nutritional tool in the treatment of hyperpermeability-associated disorders. Sponshorship: Grant and human recombinant lactoferrin donated from Agennix Inc., Houston, TX.

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Section: Discussionmentioning

confidence: 91%

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

2003

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“…In vivo data in humans indicate that increases in intestinal permeability induced by C 10 are a fraction of those seen with NSAIDs, both in magnitude as well as in respect of the time course. The increased epithelial permeability as defined by the lactulose:mannitol urinary excretion assay in healthy volunteers taking aspirin ranged from 146%-1967% [238][239][240][241] greater than control subjects, yet the increase with GIPET® was 50% (data not shown). While aspirin is not considered to be a more effective intestinal absorption promoter than C 10 , such studies suggest that the promoting actions of either monomeric, micellar or vesicular C 10 could relate to its physical interaction with the candidate drug.…”

Section: [4]mentioning

confidence: 99%

Safety and efficacy of sodium caprate in promoting oral drug absorption: from in vitro to the clinic

Maher

Leonard²,

Jacobsen

et al. 2009

Advanced Drug Delivery Reviews

189

170

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A major challenge in oral drug delivery is the development of novel dosage forms to promote absorption of poorly permeable Class III drugs across the intestinal epithelium.To date, no absorption promoter has been approved in a formulation specifically designed for oral delivery of Class III molecules. Promoters that are designated safe for human consumption have been licensed for use in a recently approved buccal insulin spray delivery system and also for many years as part of an ampicillin rectal suppository.Unlike buccal and rectal delivery, oral formulations containing absorption promoters have the additional technical hurdle whereby the promoter and payload must be coreleased in high concentrations at the small intestinal epithelium in order to generate significant but rapidly reversible increases in permeability. The most advanced promoter in the clinic is the medium chain fatty acid (MCFA), sodium caprate (C 10 ) , a compound already approved as a direct food additive. We discuss how it has evolved to a matrix tablet format suitable for administration to humans under the headings of mechanism of action at the cellular and tissue level and in vitro and in vivo efficacy and safety studies.In specific clinical examples, we review how C 10 -based formulations are being tested for oral delivery of bisphosphonates using Gastro Intestinal Permeation Enhancement Technology, GIPET® (Merrion Pharmaceuticals, Ireland) and in a related solid dose format for anti-sense oligonucleotides (ISIS Pharmaceuticals, USA).Keywords: Oral drug delivery, Sodium caprate (C 10 ), absorption promoter, drug delivery platforms, clinical trials, oral formulation, drug delivery systems.3 TJs form a barrier to the uncontrolled absorption of noxious luminal antigens (gate function), and maintain epithelial polarity (fence function) [8,9]. In general, the TJ consists of a restrictive pathway (shunt) with a sharp molecular size cut off, and a second unrestrictive pathway (small pore) that permits paracellular permeation of molecules of radii <4.0 Å [10,11]. Depending on the intestinal region, TJ pore sizes range from 6-22Å, sufficient to permit mannitol (6.7 Å) and EDTA (10.8 Å) to permeate to an extent, whereas the passage of inulin (30-40 Å) and fluorescent-dextran 4kDa (FD-4, 26 Å) is essentially impeded [12][13][14][15][16].A number of approaches have been used to promote oral delivery of Class III drugs ( Alternatively, the use of nanoparticles comprising biocompatible polymers (e.g. chitosan,polylactide-co-glycolide, starch and glucans) can protect cargoes from GI proteases, increase GI retention and promote absorption across gut associated lymphoid tissue (GALT) and to a lesser extent, enterocytes [45][46][47]. Most data on nanoparticle absorption from rodent models suggest that M cells in the follicle-associated epithelium of Peyer's patches (PP) are the favored site of uptake for particles of diameter 500nm-1000nm [45].Given the paucity of M cells in the GI tract of adults, the relevance of PP uptake remains controversial ...

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“…Por outro lado, o comprometimento da mucosa pela redução do fluxo sanguíneo provocada pelo exercício aumenta a permeabilidade intestinal através das junções comunicantes (estruturas protéicas que permitem a passagem de íons e moléculas entre células justapostas). A passagem de compostos agressivos através das junções comunicantes estimula a migração de neutrófilos (48)(49)(50)(51)(52) , que quando ativados disparam uma resposta imune local com geração de radicais livres e liberação de enzimas lisossomais, danificando ainda mais o epitélio intestinal (49,53) . Essa seqüência de eventos contribui para potencializar o aumento da permeabilidade intestinal e da resposta inflamatória, ocasionando o desenvolvimento de sintomas gastrintestinais e, em alguns casos, até endotoxemia (49,52,(54)(55)(56) .…”

Section: Redução Do Fluxo Sanguíneo Intestinalunclassified

“…A passagem de compostos agressivos através das junções comunicantes estimula a migração de neutrófilos (48)(49)(50)(51)(52) , que quando ativados disparam uma resposta imune local com geração de radicais livres e liberação de enzimas lisossomais, danificando ainda mais o epitélio intestinal (49,53) . Essa seqüência de eventos contribui para potencializar o aumento da permeabilidade intestinal e da resposta inflamatória, ocasionando o desenvolvimento de sintomas gastrintestinais e, em alguns casos, até endotoxemia (49,52,(54)(55)(56) . Também já foi demonstrado que atletas praticantes de atividades de longa duração, especialmente os ultramaratonistas, podem sofrer sangramento intestinal durante e após o exercício (12,(57)(58)(59)(60) .…”

Section: Redução Do Fluxo Sanguíneo Intestinalunclassified

Efeitos do exercício físico sobre o trato gastrintestinal

Lira

Vancini

Silva

et al. 2008

Rev Bras Med Esporte

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O impacto do exercício sobre o trato gastrintestinal (TGI), apesar de pouco investigado, é uma área de grande interesse. O exercício aeróbio intenso e de longa duração pode provocar sintomas gastrintestinais. Estes podem ser divididos em sintomas superiores (vômitos, náuseas e pirose retroesternal -azia) e inferiores (diarréia, cólica abdominal, perda de apetite, sangramento, aceleração dos movimentos intestinais e vontade de defecar). A etiologia desses sintomas durante o exercício é multifatorial e inclui a redução do fluxo sanguíneo intestinal, a liberação de hormônios gastrintestinais, o estresse mecânico sobre o TGI, a desidratação, os fatores psicológicos, a idade, o sexo, a dieta e o nível de treinamento do indivíduo. Por outro lado, o exercício de baixa intensidade tem efeito protetor sobre o TGI, principalmente com relação à predisposição a certas doenças como o câncer de cólon, a diverticulite, a colelitíase e a constipação. Diversos mecanismos são postulados para explicar os efeitos do exercício sobre o TGI, contribuindo para o desenvolvimento de estratégias terapêuticas no tratamento de indivíduos com sintomas e doenças gastrintestinais.Palavras-chave: exercício, trato gastrintestinal, sintomas gastrintestinais e doenças gastrintestinais. ABSTRACTThe impact of exercise on the gastrointestinal tract (GI tract), although being little investigated, is a field of high interest. Intense endurance aerobic exercise can lead to gastrointestinal symptoms. These symptoms can be classified into upper symptoms (vomiting, nausea and retrosternal pyrosis -heartburn) and lower symptoms (diarrhea, abdominal cramps, loss of appetite, bleeding, accelerated bowel transit time, urge to defecate). These symptoms' etiology during exercise is multifactorial and includes: reduction of intestinal blood flow, release of gastrointestinal hormones, mechanical stress on the GI tract, dehydration, psychological factors, age, gender, diet, and training status. On the other hand, low intensity exercise has a protective effect on the GI tract; mainly, with certain diseases, such as, colon cancer, diverticular disease, cholelithiases, and constipation. A variety of mechanisms have been postulated to explain the effects of exercise on the GI tract, contributing to the development of therapeutic strategies in the treatment of patients with gastrointestinal symptoms and diseases. Keywords INTRODUÇãOTradicionalmente, as pesquisas envolvendo a fisiologia do exercício se concentram nas respostas e adaptações dos sistemas respiratório, cardiovascular e muscular, já que muitos dos benefícios relacionados à saúde e qualidade de vida com a prática regular de exercício são decorrentes de respostas e adaptações nestes três sistemas orgânicos. Por outro lado, o exercício também exerce influência sobre outros sistemas que não estão diretamente relacionados com sua execução, tais como, o sistema imune (1,2) e o trato gastrintestinal (TGI). Neste contexto, o impacto do exercício sobre o TGI, apesar de pouco explorado, é uma área de grande interesse...

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Gastrointestinal permeability during exercise: effects of aspirin and energy-containing beverages

Cited by 90 publications

References 24 publications

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

Safety and efficacy of sodium caprate in promoting oral drug absorption: from in vitro to the clinic

Efeitos do exercício físico sobre o trato gastrintestinal

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