Treatment of enterogenic endotoxinemia with lactoferrin in rats

Abstract

Enterogenic endotoxinemia was induced in 28 Wistar rats by means of intraperitoneal injection of 80 mg/kg carrageenan and intraduodenal administration of 5 x 10(10)/kg Escherichia coli bacteria and 10 mg/kg nebacetin. The control group A received 600 mg/kg albumin in addition via the duodenal probe, and the groups B, C and D received 20, 40 and 80 mg/kg lactoferrin, respectively. The therapeutic effect was investigated by determining the endotoxin activity in the plasma every hour. In addition, the bacterial contamination of peritoneal lavages and mesenteric lymph nodes was checked by incubation for 48 h at 37 degrees C. The period of observation was 5 h. There was a dose-dependent improvement of the endotoxin activity in plasma and the bacterial contamination of the peritoneum cavity and mesenteric lymph nodes after lactoferrin administration. The maximum plasma endotoxin activity could be reduced by 89% with 80 mg/kg lactoferrin.

Lactoferrin-lipopolysaccharide (LPS) binding as key to antibacterial and antiendotoxic effects

“…As has been addressed in experimental animals, Lf and Lf derivatives possess protective action against systemic bacterial infections [52,53,76] as well neutralizing properties in regard to endotoxemia [61] and intestinal damage [59] caused by LPS. Taking into account the multifactorial context of sepsis, Lf would not be recommendable as a single agent for the treatment of sepsis, but its permeabilizing and endotoxin neutralizing activities make it a potential adjunctive compound for the clinical treatment of that life threatening dysfunction.…”

“…Accordingly, in the experimental model of enterogenic endotoxemia in rats infected enterically with E. coli and treated with antibiotics to promote LPS translocation, it was observed that Lf reduced LPS levels in plasma [52][53][54]. In another study with an animal model, Lf also showed the capacity to reduce inflammation at the intestinal level, thus conferring protection against diarrhea.…”

Lactoferrin: an iron-binding antimicrobial protein against Escherichia coli infection

“…In one study of ETEC strain, the bacteria counts of ETEC in various sections of intestine is lower in the bLF treatment group than in the control group, implying the inhibitory effect of LF on the adherence of ETCE to the intestinal tract (Kawasaki et al 2000). LF is able to reduce the endotoxemia and bacterial translocation to mesenteric lymph nodes and peritoneal cavity after enteral challenge of E. coli (Nebermann et al 2001).…”

Lactoferrin: Balancing Ups and Downs of Inflammation Due to Microbial Infections

“…Modulatory effects of either hLf or bLf, including derived Lfcins, on parameters associated with inflammation, has been evidenced in models of intestinal and systemic-related endotoxemia induced by LPS (also known as endotoxin) from Gram-negative enterobacteria [150,151]. These experimental models are intended to assess the impact of Lf at intestinal and systemic levels on inflammatory markers elicited by LPS that affect the gut barrier, bacterial translocation, diarrhea, tissue damage and endotoxic shock, among others [110,152,153,154,155]. In some cases, experimental assays with LPS administration encompass the use of zymosan, d -galactosamine ( d -GalN) or carrageenan to increase the sensibility of animals toward the toxic effects of low LPS doses [153,154].…”

“…LFP20 elicited the expression of tight junction proteins involved in the regulation of intestinal permeability, i.e., zonula occludens-1, occludin and claudin-1, as well as decreased colonic apoptosis [110,152,153,154,155,156,157]. Protective action of hLf on the gut barrier function against the LPS-induced intestinal damage has also been described for hLf in in vitro cultures of Caco-2 cells and jejune segments of mice underwent LPS-endotoxemia [155,158].…”