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

Abstract

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.

Phase I trial of oral talactoferrin alfa in refractory solid tumors

“…The maximally tolerated dose of talactoferrin was not reached in this study, as Grade III or IV toxicity was not encountered at any of the three dose levels. This lack of toxicity was consistent with previous experience-no drug related SAEs were observed in previous studies in healthy volunteers with doses as high as 15 g in a 24-hour period [17], and no toxicities were found in mouse and primate safety studies at doses as high as 1000 mg/kg [unpublished]. Based on previous animal work [10], the maximally efficacious dose was estimated at between 4.5 and 9 g/day.…”

The Pharmacology of Radiolabeled Cationic Antimicrobial Peptides

“…68,69 More recently, oral administration of human lactoferrin in mice 70 or recombinant human lactoferrin in humans has shown effectiveness during short-term treatment of infections or hyperpermeability-associated disorders and in the latter study lactoferrin is well tolerated up to 5 g per person. 71,72 It is now well established that when a protein is administered orally, it comes in contact with specific secondary lymphoid organs such as the tonsils and the Peyer's patches. Complex interactions that then take place in these sites are crucial for the development of a specific immune response to the antigen.…”

Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

“…Lactoferrin has been shown to prevent NSAID-induced bleeding in rodents [118] and this effect may be related to its ability to promote the growth of Bifidobacteria in the small intestine [119] . Oral treatment of healthy volunteers with recombinant lactoferrin was shown to reduce indomethacin-induced changes in small intestinal permeability [120] . However, in this short-term study, only a very modest increase in intestinal permeability was seen, with only a single administration of lactoferrin that would have been unlikely to have significantly affected the intestinal microbiome.…”