lactoferrin and Giardiasis

This study evaluates the effects of retinol on intestinal barrier function, growth, total parasites, and Giardia spp infections in children in northeastern Brazil.. The study was a double-blind, randomized placebo-controlled trial (http://clinicaltrials.gov; register no. #NCT00133406) involving 79 children who received vitamin A 100,000-200,000 IU (n = 39) or placebo (n = 40) at enrollment, 4, and 8 months and were followed for 36 months. Intestinal barrier function was evaluated using the lactulose:mannitol ratio test. Stool lactoferrin was used as a marker for intestinal inflammation.. The groups were similar with regard to age, sex, nutritional parameters (z scores), serum retinol concentrations, proportion of lactoferrin-positive stool samples, and intestinal barrier function. The lactulose:mannitol ratio did not change during the same time of follow-up (P > 0.05). The proportion of lactoferrin-positive samples evaluated at 1 month did not change between groups (P > 0.05). Total intestinal parasitic, specifically new, infections were significantly lower in the vitamin A treatment compared with control group; these were accounted for entirely by significantly fewer new Giardia infections in the vitamin A treatment group. The cumulative z scores for weight-for-length or height, length or height-for-age z scores, and weight-for-age did not change significantly with vitamin A intervention for 36 months of follow-up.. These data showed that total parasitic infection and Giardia spp infections were significantly lower in the vitamin A treatment group when compared with the placebo group, suggesting that vitamin A improves the host's defenses against Giardia infections.

Topics: Adjuvants, Immunologic; Biomarkers; Child; Child, Preschool; Dietary Supplements; Double-Blind Method; Feces; Female; Giardiasis; Growth; Humans; Inflammation; Intestinal Mucosa; Lactoferrin; Male; Protozoan Infections; Vitamin A; Vitamins

We conducted a randomized, double-blind, placebo-controlled trial comparing supplementation with bovine lactoferrin versus placebo for the prevention of diarrhea in children. Comparison of overall diarrhea incidence and prevalence rates found no significant difference between the 2 groups. However, there was a lower prevalence of colonization with Giardia species and better growth among children in the lactoferrin group.

Topics: Animals; Child, Preschool; Diarrhea; Dietary Supplements; Feces; Giardia; Giardiasis; Humans; Infant; Lactoferrin; Placebos

Lactoferrin (LF) is an 80 KDa iron-binding glycoprotein that plays a significant role in the innate immune system and is considered to be an important microbicide molecule. It has been suggested to be effective in the treatment of giardiasis, an intestinal disease caused by the protozoan parasite G. lamblia. However, the molecular mechanisms by which LF exerts its effect on this parasite are unknown. Most of the microbicidal activity of human or bovine LF (hLF or bLF) has been associated with the N-terminal region of the mature LF - lactoferricin (LFcin). LFcin is produced by pepsin cleavage of the native protein in vitro and likely in vivo. In this work, we analyse the participation of the endocytic machinery of G. lamblia in the internalization of bLF and bLFcin and their effects on cell homeostasis. Our results show that, when bLF or bLFcin are internalized by receptor-mediated endocytosis, cell growth stops, and morphological changes are produced in the trophozoites, which ultimately will produce immature cysts. Our findings contribute to disclose the fine mechanism by which bLF and bLFcin may function as an antigiardial molecule and why they have therapeutic potential to eradicate giardiasis.

Topics: Animals; Cattle; Cell Proliferation; Cells, Cultured; Cysts; Dose-Response Relationship, Drug; Endocytosis; Giardia; Giardiasis; Humans; Lactoferrin; Protein Binding; Receptors, LDL

Giardia intestinalis is the most common infectious protozoan parasite in children. Despite the effectiveness of some drugs, the disease remains a major worldwide problem. Consequently, the search for new treatments is important for disease eradication. Biological molecules with antimicrobial properties represent a promising alternative to combat pathogens. Bovine lactoferrin (bLF) is a key component of the innate host defense system, and its peptides have exhibited strong antimicrobial activity. Based on these properties, we evaluated the parasiticidal activity of these peptides on G. intestinalis. Trophozoites were incubated with different peptide concentrations for different periods of time, and the growth or viability was determined by carboxyfluorescein-succinimidyl-diacetate-ester (CFDA) and propidium iodide (PI) staining. Endocytosis of peptides was investigated by confocal microscopy, damage was analyzed by transmission and scanning electron microscopy, and the type of programmed cell death was analyzed by flow cytometry. Our results showed that the LF peptides had giardicidal activity. The LF peptides interacted with G. intestinalis and exposure to LF peptides correlated with an increase in the granularity and vacuolization of the cytoplasm. Additionally, the formation of pores, extensive membrane disruption, and programmed cell death was observed in trophozoites treated with LF peptides. Our results demonstrate that LF peptides exhibit potent in vitro antigiardial activity.

Topics: Animals; Anti-Infective Agents; Cattle; Cell Survival; Feces; Giardia lamblia; Giardiasis; Humans; Lactoferrin; Peptide Fragments; Trophozoites

Human and bovine lactoferrins and their derived N-terminal peptides were giardicidal in vitro. Fe3+, but not Fe2+, protected trophozoites from both native lactoferrin and peptides, although the latter lack iron-binding sites. Other divalent metal ions protected only against native lactoferrin. Log-phase cells were more resistant to killing than stationary-phase cells. These studies suggest that lactoferrin, especially in the form of the N-terminal peptides, may be an important nonimmune component of host mucosal defenses against Giardia lamblia.

Topics: Animals; Antiprotozoal Agents; Cations, Divalent; Cattle; Giardia lamblia; Giardiasis; Humans; Hydrogen-Ion Concentration; Lactoferrin; Metals; Peptide Fragments