lactoferrin and Body-Weight

Obesity is a strong predictive factor in the development of chronic disease and has now superseded undernutrition as a major public health issue. Chronic inflammation is one mechanism thought to link excess body weight with disease. Increasingly, the gut and its extensive population of commensal microflora are recognized as playing an important role in the development of obesity-related chronic inflammation. Obesity and a high fat diet are associated with altered commensal microbial communities and increased intestinal permeability which contributes to systemic inflammation as a result of the translocation of lipopolysaccharide into the circulation and metabolic endotoxemia. Various milk proteins are showing promise in the prevention and treatment of obesity and chronic low-grade inflammation via reductions in visceral fat, neutralization of bacteria at the mucosa and reduced intestinal permeability. In this review, we focus on evidence supporting the potential antiobesogenic and anti-inflammatory effects of bovine whey-derived lactoferrin and immunoglobulins.

Topics: Animals; Anti-Inflammatory Agents; Anti-Obesity Agents; Body Weight; Cattle; Chronic Disease; Disease Models, Animal; Endotoxemia; Functional Food; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Immunoglobulins; Inflammation; Lactoferrin; Lipopolysaccharides; Obesity; Randomized Controlled Trials as Topic; Whey

Given the role of the intestinal microbiota in obesity and related disease, strategies to modulate the composition of the intestinal microbiota may augment traditional weight-management approaches. Here, we examined the safety and tolerability of 28 days of supplementation with bovine whey-derived lactoferrin and immunoglobulin supplements in a cross-sectional cohort of free-living adults. Participants (n = 20 each group) received enteric-coated whey-derived bovine lactoferrin (200 mg), immunoglobulin (200 mg or 800 mg), combination lactoferrin/immunoglobuiln supplements (200 mg/200 mg, 200 mg/800 mg) or placebo in a double-blind design. Supplement use was generally well tolerated and routine haematology, and clinical chemistry measures were largely unchanged following supplementation. Measures of body composition remained stable and indices of glycaemic control and blood lipids revealed fluctuations of <5% but were not significantly different between groups. Overall, short-term lactoferrin/immunoglobulin supplementation was well tolerated in this cohort; use of these types of supplements to enhance other weight management strategies should be investigated over extended periods.

Topics: Adolescent; Adult; Blood Pressure; Body Composition; Body Mass Index; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Dietary Supplements; Double-Blind Method; Energy Intake; Exercise; Female; Humans; Immunoglobulins; Lactoferrin; Male; Middle Aged; Triglycerides; Waist Circumference; Young Adult

The aim of this study was to evaluate whether an iron-fortified formula with a concentration of lactoferrin would significantly improve the hematologic indexes and iron status in term infants compared with those same values in infants fed an iron-fortified formula without lactoferrin.. In this prospective, multicenter, controlled intervention study, 260 infants ages 4 to 6 mo were selected from six maternal and children's health care hospitals in the area. All infants were divided into two groups with the sequence of outpatient: lactoferrin-fortified formula milk group (fortified group, FG, containing lactoferrin 38 mg/100 g milk and iron element 4 mg/100 g milk) and no lactoferrin fortified milk (control group, CG, containing lactoferrin 0 mg/100 g milk and iron element 4 mg/100 g milk) for 3 mo. The levels of weight, height, and head circumference and the concentration of hemoglobin (Hb), serum ferritin (SF), and serum transferring receptor (sTfR) were measured and sTfR-SF index (TFR-F index), total body iron content (TBIC) and low height for age (HAZ), low weight for age (WAZ), and low weight for height (WHZ) were computed before and after the intervention, respectively.. In all, 213 (115 in FG and 98 in CG) infants completed the intervention trial and all measurements of biochemical indicators. There were no significant differences in the average amount of daily intake of formula milk (94.3 ± 9.8 g versus 88.2 ± 8.7 g for FG and CG; P > 0.05) and iron element (3.8 ± 0.4 mg versus 3.7 ± 0.6 mg for FG and CG; P > 0.05). The average amount of daily intake of lactoferrin for infants in FG group was 35.8 ± 3.7 mg. The levels of weight, WAZ, WHZ, Hb, SF, TFR-F index, and TBIC after intervention of infants in FG were all significantly higher than those of infants in CG weight, 8723 ± 245 g versus 8558 ± 214g; WAZ, 1.02 ± 0.31 versus 0.44 ± 0.18; WHZ, 0.98 ± 0.31 versus 0.41 ± 0.12; Hb, 125.5 ± 15.4 g/L versus 116.9 ± 13.1 g/L; SF, 44.7 ± 17.2 μg/L versus 31.6 ± 18.4 μg/L; TFR-F index, 1.88 ± 0.41 versus 1.26 ± 0.39; TBIC, 6.12 ± 0.78 mg/kg versus 5.26 ± 0.55 mg/kg for FG and CG; P < 0.05), but significantly lower (P < 0.05) for the prevalence of anemia (4.1% versus 7.5%), iron deficiency (13.9% versus 24.4%), and iron-deficient anemia (1.7% versus 6.1%).. When infants who were exclusively breastfed were supplemented with lactoferrin-fortified milk, significant increases in TBIC and iron absorption in the intestine were seen.

Topics: Anemia, Iron-Deficiency; Body Weight; Breast Feeding; C-Reactive Protein; Female; Follow-Up Studies; Food, Fortified; Hemoglobins; Humans; Infant; Infant Formula; Iron, Dietary; Lactoferrin; Male; Nutritional Status; Prevalence; Prospective Studies; Risk Factors; Socioeconomic Factors; Surveys and Questionnaires; Treatment Outcome

Lactoferrin (LF), a multifunctional glycoprotein in mammalian milk, is reported to exert a modulatory effect on lipid metabolism. The aim of the present study was to elucidate whether enteric-coated LF (eLF) might improve visceral fat-type obesity, an underlying cause of the metabolic syndrome. Using a double-blind, placebo-controlled design, Japanese men and women (n 26; aged 22-60 years) with abdominal obesity (BMI>25 kg/m2, and visceral fat area (VFA)>100 cm2) consumed eLF (300 mg/d as bovine LF) or placebo tablets for 8 weeks. Measurement of the total fat area, VFA and subcutaneous fat area from computed tomography images revealed a significant reduction in VFA ( - 14.6 cm2) in the eLF group, as compared with the placebo controls ( - 1.8 cm2; P = 0.009 by ANCOVA). Decreases in body weight, BMI and hip circumference in the eLF group ( - 1.5 kg, - 0.6 kg/m2, - 2.6 cm) were also found to be significantly greater than with the placebo (+1.0 kg, +0.3 kg/m2, - 0.2 cm; P = 0.032, 0.013, 0.041, respectively). There was also a tendency for a reduction in waist circumference in the eLF group ( - 4.4 cm) as compared with the placebo group ( - 0.9 cm; P = 0.073). No adverse effects of the eLF treatment were found with regard to blood lipid or biochemical parameters. From these results, eLF appears to be a promising agent for the control of visceral fat accumulation.

Topics: Adiposity; Adult; Anti-Obesity Agents; Asian People; Body Mass Index; Body Weight; Double-Blind Method; Female; Hip; Humans; Intra-Abdominal Fat; Lactoferrin; Male; Middle Aged; Obesity, Abdominal; Tablets, Enteric-Coated; Tomography, X-Ray Computed; Waist Circumference; Young Adult

Sixty Holstein calves (30 bulls, 30 heifers) were used to examine the effects of supplemental lactoferrin on feed intake, growth, and health during the preweaning and postweaning periods. One of 3 levels of lactoferrin was supplemented from 3 to 56 d in either whole milk or water to produce 3 dietary treatments: 1) 0 g/d, 2) 0.5 g/d, and 3) 1 g/d. Whole milk (3.8 L/d) containing lactoferrin supplements was fed from bottles until weaning at 35 d. From d 36 to 56, lactoferrin supplements were added to water (15 to 25 mL) and fed from bottles. Lactoferrin supplementation had no effect on feed intake, body weight, average daily gain, heart girth, body temperature, fecal scores, respiratory scores, or haptoglobin concentrations. Calves were housed in individual pens in either an open-sided barn or hutches. Calves raised in the barn consumed more calf starter and therefore grew better than calves raised in hutches. Under the conditions of this study, lactoferrin supplementation was not beneficial. Further research is needed to fully elucidate the role of lactoferrin, and possible benefits during different feeding conditions or milk sources.

Topics: Animal Feed; Animals; Body Constitution; Body Temperature; Body Weight; Cattle; Diet; Dietary Supplements; Eating; Female; Haptoglobins; Health Status; Housing, Animal; Immunization, Passive; Lactoferrin; Least-Squares Analysis; Male; Respiration; Weaning

Elucidating the mechanisms of bacterial translocation is crucial for the prevention and treatment of neonatal sepsis. In the present study, we aimed to evaluate the potential of lactoferrin to inhibit the development of late-onset blood infection in neonates. Our investigation evaluates the role of key stress factors leading to the translocation of intestinal bacteria into the bloodstream and, consequently, the development of life-threatening sepsis. Three stress factors, namely weaning, intraperitoneal administration of Gram-positive cocci and oral intake of Gram-negative rods, were found to act synergistically. We developed a novel model of rat pups sepsis induced by bacterial translocation and observed the inhibition of this process by supplementation of various forms of lactoferrin: iron-depleted (apolactoferrin), iron-saturated (hololactoferrin) and manganese-saturated lactoferrin. Additionally, lactoferrin saturated with manganese significantly increases the

Topics: Animals; Animals, Newborn; Apoproteins; Bacterial Translocation; Blood-Borne Infections; Body Temperature; Body Weight; Cross Infection; Disease Models, Animal; Drug Administration Schedule; Escherichia coli; Gastrointestinal Microbiome; Humans; Infant, Newborn; Lactoferrin; Male; Manganese; Neonatal Sepsis; Permeability; Random Allocation; Rats; Rats, Wistar; Staphylococcus haemolyticus; Weaning

Lactoferrin (LF) is an iron-binding protein found at relatively high concentrations in human milk. LF, which is little degraded in the infant intestinal lumen, is known to stimulate the proliferation and differentiation of the small intestine epithelial cells. The present study was designed to evaluate in the rat model the effects of bovine LF (bLF) given to the mothers during gestation and lactation on the growth of the offspring. Female Wistar rats were randomly separated into two groups of animals that received from mating and during gestation and lactation a standard diet including or not including bLF (10 g/kg of diet). The pups' growth was determined up to postnatal day 17 (PND17), and parameters related to lean and fat mass, intestinal differentiation, intestinal barrier function, bone mineral density, osteoblast activity, and brain development were measured. In addition, metabolites in pup plasma were determined at PND17. bLF was detected in the plasma and milk of the supplemented mothers as well as in the pup plasma. Although the body weight of the pups in the two groups did not differ at birth, the pups recovered from the supplemented mothers displayed an increase body weight from PND12 up to PND17. At PND17 in the bLF group, increased small intestine epithelial cell differentiation was detected, and colon barrier function was reinforced in association with increased expression of genes coding for the tight-junction proteins. Regarding bone physiology, improved bone mineral density was measured in the pups. Lastly, the plasma metabolite analysis revealed mainly higher amino acid concentrations in the LF pups as compared to the control group. Our results support that bLF ingestion by the mother during gestation and lactation can promote pup early life development. The potential interest of supplementing the mothers with bLF in the case of risk of compromised early life development of the offspring in the context of animal and human nutrition is discussed.

Topics: Animals; Body Weight; Cattle; Dietary Supplements; Female; Lactation; Lactoferrin; Pregnancy; Rats; Rats, Wistar

Aflatoxin M1 (AFM1), the only toxin with maximum residue levels in milk, has adverse effects on the intestinal barrier, resulting in intestinal inflammatory disease. Lactoferrin (LF), one of the important bioactive proteins in milk, performs multiple biological functions, but knowledge of the protective effects of LF on the compromised intestinal barrier induced by AFM1 has not been investigated. In the present study, results using Balb/C mice and differentiated Caco-2 cells showed that LF intervention decreased AFM1-induced increased intestinal permeability, improved the protein expression of claudin-3, occludin and ZO-1, and repaired the injured intestinal barrier. The transcriptome and proteome were used to clarify the underlying mechanisms. It was found that LF reduced the intestinal barrier dysfunction caused by AFM1 and was associated with intestinal cell survival related pathways, such as cell cycle, apoptosis and MAPK signaling pathway and intestinal integrity related pathways including endocytosis, tight junction, adherens junction and gap junction. The cross-omics analysis suggested that insulin receptor (INSR), cytoplasmic FMR1 interacting protein 2 (CYFIP2), dedicator of cytokinesis 1 (DOCK1) and ribonucleotide reductase regulatory subunit M2 (RRM2) were the potential key regulators as LF repaired the compromised intestinal barrier. These findings indicated that LF may be an alternative treatment for the compromised intestinal barrier induced by AFM1.

Topics: Aflatoxin M1; Animals; Body Weight; Caco-2 Cells; Cell Membrane Permeability; Claudin-3; Gene Expression Profiling; Gene Expression Regulation; Humans; Intestines; Lactoferrin; Male; Mice; Mice, Inbred BALB C; Occludin; Proteome; RNA, Messenger; Transcriptome; Zonula Occludens-1 Protein

Lactoferrin (Lf), a sialylated milk glycoprotein, promotes early neurodevelopment and cognition. Functional concentrations of Lf, however, remain unknown. Our objective is to determine the concentration-dependency of Lf on genes associated with neurodevelopment and cognition in neonatal piglets.. Piglets are given milk replacer with Lf at concentrations of 155 (low) or 285 mg kg. The lower concentrations of Lf enhanced neurodevelopment and cognition, while higher concentrations are greater neuroprotective, findings of potential novel clinical relevance.

Topics: Adrenocorticotropic Hormone; Animals; Animals, Newborn; Body Weight; Brain-Derived Neurotrophic Factor; Cognition; Dose-Response Relationship, Drug; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Hippocampus; Hydrocortisone; Lactoferrin; Learning; Male; Memory, Long-Term; Swine

The aim of the study was to compare serum lactoferrin concentrations in metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) women.. Three hundred (101 MHO and 199 MUHO) women were recruited to the study. Basic anthropometric parameters and blood pressure were measured. Body mass index (BMI) was calculated. Fat mass and visceral adipose tissue mass were assessed using dual X-ray absorptiometry scan. Fasting glucose, insulin, lipid profile, high sensitivity C-reactive protein (hs-CRP) and lactoferrin levels were determined.. Lactoferrin levels did not differ between MHO and MUHO subjects (median (interquartile range): 1639 (1055-2396) vs. 1622 (1009-23345) ng/mL). However, in the total population insulin (r = 0.131,. Lactoferrin levels did not differ between MHO and MUHO women. However, some mild correlations between lactoferrin concentrations and anthropometric and metabolic parameters were observed mostly in MHO subjects.

Topics: Adiposity; Biomarkers; Body Mass Index; Body Weight; Energy Metabolism; Female; Humans; Lactoferrin; Middle Aged; Obesity; Obesity, Metabolically Benign; Waist Circumference

To date, many safety assessments of genetically modified (GM) food have been done, but there was still considerable skepticism about the safety of genetic modified foods because no study could be designed to discover all of the potential effects. Since behavioral endpoints could provide one of the most sensitive strategies to reveal subtle functional deficits. In the present study, behavioral profiles in mice fed with milk derived from human lactoferrin gene-modified cows were investigated to enrich the toxicological data of GM food. Conventional milk and GM milk were added to diets at a proportion of 7.5%, 15% and 30%(w/w). After the mice consuming different diets for 30 days, a battery of behavioral tests were conducted to evaluate motor, sensory and cognitive functions. No significant differences were observed in spontaneous activity, grip strength and nociception between the treatment groups. And animals of different groups exhibited similar performance in rotarod, dark box, step-down and MORRIS water maze task. The study suggested that mice fed with conventional milk or human lactoferrin gene-modified milk had similar motor, sensory and cognitive functions.

Topics: Animal Feed; Animals; Behavior, Animal; Body Weight; Cattle; Dietary Supplements; Female; Humans; Lactoferrin; Mice; Mice, Inbred Strains; Milk

The inherent disease susceptibility of veal calves results in frequent antimicrobial use. Improvements in antimicrobial stewardship necessitate alternative therapies to improve calf health and growth, while reducing the need for antimicrobials important to human health. This study investigated the effect of 2 alternative therapies, lactoferrin (an iron-binding protein found in colostrum) and cinnamaldehyde (an essential oil of the cinnamon plant) on growth, disease incidence, and mortality risk in special-fed veal calves. On the day of arrival to the growing facility (3 to 7 d of age), calves (n = 80 per treatment) were randomized to 1 of 3 treatments: (1) control (no supplement), (2) lactoferrin (1 g/d in milk replacer for 7 d), or (3) cinnamaldehyde (1 g/d in milk replacer for 21 d). Body weight was measured on the day of arrival (d 0), 21, and 42 d postarrival. Health assessments were performed twice weekly through 21 d, and mortality records were obtained through 6 wk postarrival. A repeated-measures ANOVA was used to compare growth between treatment groups, and a Poisson regression model (PROC GENMOD, SAS v. 9.4, SAS Institute Inc., Cary, NC) was used to test differences between groups in the incidence of diarrhea (fecal score ≥2 with and without depression and temperature) and disease through 3 wk postarrival. Body weight and average daily gain were similar between treatments. Neither lactoferrin nor cinnamaldehyde had an effect on diarrhea incidence. However, the risk of navel inflammation was significantly lower for calves that received cinnamaldehyde compared with calves in the control group. Mortality through 6 wk postarrival was low, with 4, 1, and 0 deaths from the control, lactoferrin, and cinnamaldehyde treatment groups, respectively. Additional research is needed to investigate various doses of these alternative therapies on calf health and growth, in addition to different routes of administration.

Topics: Acrolein; Animal Feed; Animals; Anti-Bacterial Agents; Body Weight; Cattle; Cattle Diseases; Colostrum; Diarrhea; Diet; Dietary Supplements; Female; Health Status; Inflammation; Lactoferrin; Milk; Weight Gain

BackgroundLactoferrin (LTF) could play a beneficial role in insulin resistance and diabetes, but the association of its gene variants with cardio-metabolic disorders in children has not been investigated. This study aimed to examine the relationship between LTF variants, plasma LTF concentrations, and cardio-metabolic risk factors in French-Canadian children.MethodsThe study cohort comprises 1,749 French Canadians aged 9, 13, and 16 years. The association of 13 LTF polymorphisms, metabolic parameters, and plasma LTF levels was tested in this cross-sectional, province-wide school-based survey.ResultsNone of the genetic association remained significant after correction for multiple testing and LTF SNPs were not associated with LTF levels. Plasma LTF was positively correlated with body mass index (r

Topics: Adolescent; Age Factors; Body Mass Index; Body Weight; Child; Cross-Sectional Studies; Female; Genetic Predisposition to Disease; Haplotypes; Health Surveys; Humans; Lactoferrin; Lipids; Male; Metabolic Syndrome; Phenotype; Polymorphism, Single Nucleotide; Quebec; Risk Factors; Sex Factors

Whey protein promotes weight loss and improves diabetic control, however, less is known of its bioactive components that produce such benefits. We compared the effects of normal protein (control) diet with high protein diets containing whey, or its fractions lactalbumin and lactoferrin, on energy balance and metabolism. Diet-induced obese rats were randomized to isocaloric diets: Control, Whey, Lactalbumin, Lactoferrin, or pair-fed to lactoferrin. Whey and lactalbumin produced transient hypophagia, whereas lactoferrin caused prolonged hypophagia; the hypophagia was likely due to decreased preference. Lactalbumin decreased weight and fat gain. Notably, lactoferrin produced sustained weight and fat loss, and attenuated the reduction in energy expenditure associated with calorie restriction. Lactalbumin and lactoferrin decreased plasma leptin and insulin, and lactalbumin increased peptide YY. Whey, lactalbumin and lactoferrin improved glucose clearance partly through differential upregulation of glucoregulatory transcripts in the liver and skeletal muscle. Interestingly, lactalbumin and lactoferrin decreased hepatic lipidosis partly through downregulation of lipogenic and/or upregulation of β-oxidation transcripts, and differentially modulated cecal bacterial populations. Our findings demonstrate that protein quantity and quality are important for improving energy balance. Dietary lactalbumin and lactoferrin improved energy balance and metabolism, and decreased adiposity, with the effects of lactoferrin being partly independent of caloric intake.

Topics: Adiposity; Animals; Body Weight; Diet; Energy Intake; Energy Metabolism; Insulin; Lactalbumin; Lactoferrin; Leptin; Male; Obesity; Peptide YY; Rats; Whey Proteins

Lactoferrin (LF), a sialylated iron-binding glycoprotein, performs multiple beneficial functions including modulating immunity and improves neurodevelopment, health and growth performance. Maternal LF intervention for gilts (first parity sows) on the performance of gilts and their offspring remains unknown. In the current study gilts were fed with a commercial pig feed supplemented with 1g LF /day (treatment group) or 1g milk casein/day (control group) from day 1 post mating throughout pregnancy and lactation for about 135 days. The milk production and body weight gain was monitored. The immunoglobulin concentrations in the serum of gilts and piglets were measured using ELISA. Our study showed that maternal LF supplementation to the gilt (1) significantly increased milk production at different time points (day 1, 3, 7 and 19) of lactation compared to the control (p<0.001); (2) significantly increased body weight gain of their piglets during the first 19 days of life compared to the control group (p<0.05); (3) tended to increase pregnancy rate, litter size and birth weight, number of piglets born alive, and decrease the number of dead and intrauterine growth restriction (IUGR) piglets; (4) significantly increased the concentration of serum IgA in gilt and serum sIgA in piglet (p<0.05). In summary, maternal Lf intervention in gilts can improve milk production, pig production and serum IgA and sIgA levels, and therefore plays a key role in shaping the performance of their progeny.

Topics: Animal Feed; Animals; Body Weight; Caseins; Female; Lactation; Lactoferrin; Pregnancy; Swine

The antimicrobial substances in saliva contribute to the maintenance of both oral health and overall health of the body. Therefore, the associations among immunoglobulin A (IgA), lactoferrin and lysozyme flow rates in the saliva of children, and their relationships with the physical attributes and lifestyle factors of children, were examined.. Saliva was collected from 90 children who visited the Kanagawa Dental University Hospital Pediatric Dentistry, and questionnaires were completed by guardians. IgA, lactoferrin and lysozyme concentrations were measured in the saliva samples using enzyme-linked immunosorbent assays (ELISAs).. The IgA flow rate in saliva increased as age, height and weight increased. A correlation was found between lactoferrin and lysozyme flow rates. When the antimicrobial substance flow rates in the saliva were divided into two groups of 22 children each based on the highest and lowest quartiles, children with either a low or high IgA flow rate also had a high or low lactoferrin flow rate, respectively. The same pattern was observed for lactoferrin and lysozyme flow rates.. There is a high probability that the IgA flow rate in the saliva of children reflects and corresponds to the developmental status of immune function as the child ages and increases in height and weight. The flow rates of lactoferrin and lysozyme were correlated in children. In addition, regarding lifestyle factors, the duration of sleep and lactoferrin flow rate were also related.

Topics: Adolescent; Age Factors; Anti-Infective Agents; Body Height; Body Weight; Child; Child, Preschool; Cross-Sectional Studies; Feeding Behavior; Female; Humans; Immunoglobulin A, Secretory; Lactoferrin; Life Style; Male; Muramidase; Oral Health; Saliva; Salivary Proteins and Peptides; Secretory Rate; Sleep

Lactoferrin (Lf) is a sialic acid (Sia)-rich, iron-binding milk glycoprotein that has multifunctional health benefits. Its potential role in neurodevelopment and cognition remains unknown. To test the hypothesis that Lf may function to improve neurodevelopment and cognition, the diet of postnatal piglets was supplemented with Lf from days 3 to 38. Expression levels of selected genes and their cognate protein profiles were quantitatively determined. The importance of our new findings is that Lf (1) upregulated several canonical signaling pathways associated with neurodevelopment and cognition; (2) influenced ~10 genes involved in the brain-derived neurotrophin factor (BDNF) signaling pathway in the hippocampus and upregulated the expression of polysialic acid, a marker of neuroplasticity, cell migration and differentiation of progenitor cells, and the growth and targeting of axons; (3) upregulated transcriptional and translational levels of BDNF and increased phosphorylation of the cyclic adenosine monophosphate (cAMP) response element-binding protein, CREB, a downstream target of the BDNF signaling pathway, and a protein of crucial importance in neurodevelopment and cognition; and (4) enhanced the cognitive function and learning of piglets when tested in an eight-arm radial maze. The finding that Lf can improve neural development and cognition in postnatal piglets has not been previously described.

Topics: Animals; Animals, Newborn; Body Weight; Brain-Derived Neurotrophic Factor; Cattle; Cognition; Gene Expression Profiling; Gene Expression Regulation, Developmental; Hippocampus; Hydrocortisone; Lactoferrin; Male; Memory; N-Acetylneuraminic Acid; Nerve Growth Factors; Nervous System; Neuronal Plasticity; Oligonucleotide Array Sequence Analysis; Signal Transduction; Sus scrofa; Transcription, Genetic; Up-Regulation

There is increasing concern about welfare of laying hens in cages, and one aspect of this topic relates to bone fragility. Therefore, bone anabolic components such as bovine lactoferrin (bLF) may be an effective strategy to maintain the integrity and health of bones. A total of 1080 eggs were divided into four groups with three replicates, each comprising 270 eggs; (1) control group was injected with 100 μl of normal saline per egg; (2, 3 and 4) groups including 22.5 (low), 45 (medium) and 67.5 µg (high) of bLF in 100 µl of normal saline per egg. Eggs were incubated and after hatching, chicks were reared to 28 weeks of age. Tibia measurements were obtained at hatch and at 28 weeks of age. Tibia weight at hatch, was not influenced by in ovo injection of bLF in comparison with the control. Eggs injected with the high concentration of bLF (67.5 µg of bLF per egg) showed significant strengthening in laying-hen tibias at 28 weeks of age, as measured by ultimate force and bending stress, compared with the control. Egg weights from hens treated with this concentration of bLF were also significantly greater than the control. Our data suggest that tibia cortical thickness is a suitable variable for evaluating bone status reflecting bone integrity and strength. The present study also shows that bLF (67.5 µg of bLF per egg) injected into layer breeder eggs before incubation can be used to improve bone strength and egg weight of laying hens at 28 weeks of age, while having no detrimental effect on embryo hatchability.

Topics: Animals; Biomechanical Phenomena; Body Weight; Cattle; Chick Embryo; Chickens; Female; Injections; Lactoferrin; Tibia

Intrauterine growth restriction (IUGR) is a major risk factor for both perinatal and long-term morbidity. Bovine lactoferrin (bLf) is a major milk glycoprotein considered as a pleiotropic functional nutrient. The impact of maternal supplementation with bLf on IUGR-induced sequelae, including inadequate growth and altered cerebral development, remains unknown.. IUGR was induced through maternal dexamethasone infusion (100 μg/kg during last gestational week) in rats. Maternal supplementation with bLf (0.85% in food pellet) was provided during both gestation and lactation. Pup growth was monitored, and Pup brain metabolism and gene expression were studied using in vivo (1)H NMR spectroscopy, quantitative PCR, and microarray in the hippocampus at postnatal day (PND)7.. Maternal bLf supplementation did not change gestational weight but increased the birth body weight of control pups (4%) with no effect on the IUGR pups. Maternal bLf supplementation allowed IUGR pups to recover a normalized weight at PND21 (weaning) improving catch-up growth. Significantly altered levels of brain metabolites (γ-aminobutyric acid, glutamate, N-acetylaspartate, and N-acetylaspartylglutamate) and transcripts (brain-derived neurotrophic factor (BDNF), divalent metal transporter 1 (DMT-1), and glutamate receptors) in IUGR pups were normalized with maternal bLf supplementation.. Our data suggest that maternal bLf supplementation is a beneficial nutritional intervention able to revert some of the IUGR-induced sequelae, including brain hippocampal changes.

Topics: Animals; Body Weight; Brain; Dexamethasone; Dietary Supplements; Female; Fetal Growth Retardation; Gene Expression; Growth; Lactation; Lactoferrin; Polymerase Chain Reaction; Pregnancy; Rats; Weight Gain

The influence of a host defense protein, lactoferrin (LF), contained in exocrine secretions such as milk, on radiation disorder was investigated. A total of 25 C3H/He mice in each of two groups were maintained with 0.1% LF-added and LF-free diets, respectively, for one month. The mice were then treated with single whole-body X-ray irradiation at a sublethal dose (6.8 Gy), and the survival rate after irradiation was investigated. The survival rate at 30 d after irradiation was relatively higher in the LF group than in the control group (LF-free), (85 and 62%, respectively). The body weight 15 d after X-ray irradiation was also significantly greater in the LF group than in the control group. The hemoglobin level and hematocrit value were higher in the LF group at 5 d before X-ray irradiation. Another 52 mice underwent whole-body X-ray irradiation at the sublethal dose (6.8 Gy), and then LF was intraperitoneally injected once at 4 mg/animal to half of them. The survival rate in LF-treated mice 30 d after irradiation was 92%, significantly higher than in mice treated with saline (50%) (P = 0.0012). In addition, LF showed hydroxyl radical scavenger activity in vitro. These findings suggest that LF may inhibit radiation damage.

Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Lactoferrin; Male; Mice; Mice, Inbred C3H; Radiation Injuries; Radiation-Protective Agents; Reactive Oxygen Species; Survival Rate

Liver diseases, which can be caused by alcohol abuse, chemical intoxication, viral hepatitis infection, and autoimmune disorders, are a significant health issue because they can develop into liver fibrosis and cirrhosis. Lactoferrin (LF), a siderophilic protein with 2 iron-binding sites, has been demonstrated to possess a multitude of biological functions, including antiinflammation, anticancer, and antimicrobial effects, as well as immunomodulatory-enhancing functions. In the current study, we induced hepatotoxicity in rats with dimethylnitrosamine (DMN) to establish a situation that would enable us to evaluate the hepatoprotective effects of LF against hepatic injury. Our results showed that DMN-induced hepatic pathological damage significantly decreased the body weight and liver index, increased the mRNA and protein levels of collagen α-1(I) (ColIα-1) and α-smooth muscle actin, and increased the hydroxyproline content. However, treatment with LF significantly increased body weight and liver index, decreased the mRNA and protein levels of ColIα-1 and α-smooth muscle actin, and suppressed the hydroxyproline content when compared with the DMN-treated group. Liver histopathology also showed that low-dose LF (100mg/kg of body weight) or high-dose LF (300 mg/kg of body weight) could significantly reduce the incidences of liver lesions induced by DMN. These results suggest that the LF exhibits potent hepatoprotection against DMN-induced liver damage in rats and that the hepatoprotective effects of LF may be due to the inhibition of collagen production and to stellate cell activation.

Topics: Animals; Body Weight; Dimethylnitrosamine; Disease Models, Animal; Hydroxyproline; Lactoferrin; Liver; Liver Cirrhosis; Male; Rats; Rats, Sprague-Dawley; RNA, Messenger; Ultrasonography

The molecular mechanisms underlying how dietary lactoferrin (Lf) impacts gut development and maturation and protects against early weaning diarrhea are not well understood. In this study, we supplemented postnatal piglets with an Lf at a dose level of 155 and 285 mg/kg/day from 3 to 38 days following birth. Our findings show that the high dose of Lf up-regulated messenger RNA expression levels of genes encoding brain-derived neurotrophic factor (BDNF) and ubiquitin carboxy-terminal hydrolase L1 (ubiquitin thiolesterase (UCHL1) and, to a lesser extent, glial cell line-derived neurotrophic factor, in the duodenum (P<.05). Piglets in the high and low Lf group had 30% and 7% larger jejunal crypts compared with the control group (P<.05). Escherichia coli 16S rRNA copy number per gram of ascending colon contents was significantly reduced (P=.001), while the copy number of Bifidobacteria and Lactobacillus spp. was not affected. In addition, Lf increased intestinal alkaline phosphatase activity (P<.05) and delayed the onset of food transitional diarrhea, reducing its frequency and duration (P<.05). The incidence of diarrhea in the high and low Lf groups was decreased 54% and 15%, respectively, compared with the control group (P=.035). In summary, these findings provide new evidence that dietary Lf supplementation up-regulated gene expression of BDNF and UCHL1, decreased the colon microbiota of E. coli, improved gut maturation and reduced early weaning diarrhea in piglets. The molecular basis underlying these findings suggests that Lf may enhance gut development and immune function by providing new insight into the gut-brain-microbe axis that has not been previously reported.

Topics: Alkaline Phosphatase; Animals; Body Weight; Brain-Derived Neurotrophic Factor; Colon; Diarrhea; Dietary Supplements; Duodenum; Gene Expression Regulation; Intestinal Mucosa; Intestines; Jejunum; Lactase; Lactoferrin; Male; Sus scrofa; Ubiquitin Thiolesterase; Up-Regulation; Weaning

Colorectal cancer is a significant source of morbidity and mortality in the United States and other Western countries. Oral delivery of therapeutics remains the most patient accepted form of medication. The development of an oral delivery formulation for local delivery of chemotherapeutics in the gastrointestinal tract can potentially alleviate the adverse side effects including systemic cytotoxicity, as well as focus therapy to the lesions. Here we develop an oral formulation of the chemotherapeutic drug oxaliplatin for the treatment of colorectal cancer. Oxaliplatin was encapsulated in pH sensitive, mucoadhesive chitosan-coated alginate microspheres. The microparticles were formulated to release the chemotherapeutics after passing through the acidic gastric environment thus targeting the intestinal tract. In vivo, these particles substantially reduced the tumor burden in an orthotopic mouse model of colorectal cancer, and reduced mortality.

Topics: Administration, Oral; Animals; Body Weight; C-Reactive Protein; Colorectal Neoplasms; Drug Compounding; Immunohistochemistry; Lactoferrin; Male; Mice; Mice, Inbred C57BL; Organoplatinum Compounds; Oxaliplatin

Doxorubicin is a potent anticancer drug and a major limiting factor that hinders therapeutic use as its high levels of systemic circulation often associated with various off-target effects, particularly cardiotoxicity. The present study focuses on evaluation of the efficacy of doxorubicin when it is loaded into the protein nanoparticles and delivered intravenously in rats bearing Hepatocellular carcinoma (HCC). The proteins selected as carrier were Apotransferrin and Lactoferrin, since the receptors for these two proteins are known to be over expressed on cancer cells due to their iron transport capacity.. Doxorubicin loaded apotransferrin (Apodoxonano) and lactoferrin nanoparticles (Lactodoxonano) were prepared by sol-oil chemistry. HCC in the rats was induced by 100 mg/l of diethylnitrosamine (DENA) in drinking water for 8 weeks. Rats received 5 doses of 2 mg/kg drug equivalent nanoparticles through intravenous administration. Pharmacokinetics and toxicity of nanoformulations was evaluated in healthy rats and anticancer activity was studied in DENA treated rats. The anticancer activity was evaluated through counting of the liver nodules, H & E analysis and by estimating the expression levels of angiogenic and antitumor markers.. In rats treated with nanoformulations, the numbers of liver nodules were found to be significantly reduced. They showed highest drug accumulation in liver (22.4 and 19.5 µg/g). Both nanoformulations showed higher localization compared to doxorubicin (Doxo) when delivered in the absence of a carrier. Higher amounts of Doxo (195 µg/g) were removed through kidney, while Apodoxonano and Lactodoxonano showed only a minimal amount of removal (<40 µg/g), suggesting the extended bioavailability of Doxo when delivered through nanoformulation. Safety analysis shows minimal cardiotoxicity due to lower drug accumulation in heart in the case of nanoformulation.. Drug delivery through nanoformulations not only minimizes the cardiotoxicity of doxorubicin but also enhances the efficacy and bioavailability of the drug in a target-specific manner.

Topics: Administration, Intravenous; Animals; Antineoplastic Agents; Apoproteins; Biomarkers; Body Weight; Carcinoma, Hepatocellular; Disease Models, Animal; Doxorubicin; Hemolysis; Lactoferrin; Liver Neoplasms; Male; Nanoparticles; Rats; Transferrin; Tumor Necrosis Factor-alpha

Lactoferrin (LF) has in vitro antimicrobial activity against Gram-negative bacteria. Salmonella enterica subsp. enterica serovar Typhimurium causes systemic infection and acute diarrhea in humans, mainly in children younger than 2 years of age. The aim of the study was to determine the in vivo effect of bovine LF in Salmonella ser. Typhimurium infection in mice. 58 BALB/c mice were employed. Two hours before the infection with 300 microl of 10(7) CFU of Salmonella ser. Typhimurium, 29 mice received LF (2 mg) and 29 placebo (buffer). After the infection, the mice received LF (10 mg/ml) ad libitum or buffer, respectively, for 7 days. Mortality, weight and clinical signs (piloerection, hunched position and reduced movement) were monitored daily. The degree of inflammation and necrosis in the intestine, liver, spleen and brain were studied with a blinded observer. The mortality in the control group (8/29) was higher than in the LF group (1/29) (Kapplan Meier P < 0.05). From the third day post-infection the control group were significantly more symptomatic (P < 0.05). The blood culture for Salmonella spp. was positive for all mice studied in the control group (17/17), but positive in the LF group in only 6/17 animals (P < 0.05). In the LF group, the pathologic studies show less inflammation and focal necrosis in the four organs studied, with the greatest difference found in the intestine. Bovine LF protects against Salmonella ser. Typhimurium infection in mice, reducing the severity, mortality and the degree of inflammation of this infection.

Topics: Animals; Anti-Bacterial Agents; Body Weight; Cattle; Female; Inflammation; Lactoferrin; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Salmonella Infections, Animal; Salmonella typhimurium; Survival Rate

Nosocomial infection with antibiotic-resistant strains is a major threat to critical care medicine. Selective decontamination of the digestive tract (SDD) is one of the strategies used to reduce ventilator-associated pneumonia and sepsis in critically ill patients. In the present study, we performed pathogenic challenges of the digestive tract in a transgenic milk-fed animal model to test whether porcine lactoferrin (pLF) is an effective SDD regimen.. Transgenic mice expressing recombinant pLF in their milk at a mean+/-SD concentration of 120+/-13.6 mg/L during the lactation stage fed normal CD-1 mice pups for 4 weeks. The pups were subsequently challenged with pathogenic Escherichia coli, Staphylococcus aureus, and Candida albicans.. Compared with the control groups fed wild-type (normal) milk, the groups fed pLF-enriched milk demonstrated statistically significant improvements in weight gain; lower bacterial numbers in intestinal fluid, blood, and liver; healthier microvilli in the small intestine; and alveoli in the lungs.. Our results showed that oral administration of pLF-enriched milk to mice led to broad-spectrum antimicrobial activity in the digestive tract and protected the mucosa of the small intestine from injury, implying that pLF can be used as an effective SDD regimen.

Topics: Animals; Animals, Newborn; Bacteremia; Bacterial Infections; Body Weight; Candidiasis; Cytokines; Escherichia coli Infections; Gastrointestinal Tract; Immunohistochemistry; Intestines; Lactation; Lactoferrin; Lung; Mice; Mice, Transgenic; Milk; Polymerase Chain Reaction; Recombinant Proteins; Staphylococcal Infections; Swine

Dextran sulfate sodium (DSS) induced intestinal inflammation is characterized by pronounced mucosal and epithelial cell damage. Bovine lactoferrin (bLf), a common dietary protein, influences inflammatory cytokines and intestinal lymphocyte (IL) apoptosis. The objectives of this study were to determine if 1) DSS induces IL necrotic or apoptotic death, 2) dietary bLf affects DSS induced IL death and 3) bLf alters cytokine profiles during DSS induced inflammation. Female C57BL/6 mice were randomized to 2% or 0% bLf diets for 12 d and within diets to 5% or 0% DSS in the drinking water for 4 d after which intestinal histology, IL number, IL apoptosis/necrosis, IL phenotypes, protein levels of pro-inflammatory cytokine (TNF-alpha) and transcription factor (NFkappaB), apoptotic (caspase 3, Bax) proteins, anti-inflammatory cytokine (IL-10) and anti-apoptotic (Bcl-2) protein in IL were evaluated. DSS treatment resulted in shortened intestinal length, decreased body weight and widespread mucosal damage as well as increased IL death as determined by a decreased percentage of viable (PI-/ANN-, P<0.005) and increased percentage of necrotic/late apoptotic (PI+/ ANN+, P<0.05) and necrotic (PI+/ANN-, P<0.05) IL. DSS exposure increased caspase 3 (P<0.05) and decreased Bcl-2 (P<0.01) protein levels in mouse IL. Dietary bLf did not influence these cell death outcome measures. However, bLf reduced protein levels of the pro-inflammatory transcription factor, NFkappaB, in IL (P<0.05) and was associated with a 34%, albeit non-significant, reduction in TNF-alpha relative to non-bLf fed mice. DSS treatment increased apoptosis and necrosis of mouse IL and elevated pro-apoptotic and reduced anti-apoptotic protein levels in these cells. Dietary bLf did not influence necrosis or apoptosis of IL but may provide limited protection in the intestine by affecting the pro-inflammatory transcription factor NFkappaB, and potentially, cytokine expression.

Topics: Animal Feed; Animals; Apoptosis; Body Weight; Caspase 3; Cattle; Dextran Sulfate; Eating; Female; Inflammatory Bowel Diseases; Interleukin-10; Lactoferrin; Lymphocytes; Mice; Mice, Inbred C57BL; NF-kappa B; Phenotype; Proto-Oncogene Proteins c-bcl-2; Tumor Necrosis Factor-alpha

Recombinant human holo-lactoferrin (holo-rhLF) was orally administered, via gavage, to Wistar rats at 1000, 500 and 100mg/kgbw/day for 28 days. The test article, holo-rhLF, was expressed in rice grain, extracted, purified and saturated with iron. During the 28-day period, animals were examined for evidence of toxicity. On day 29, the animals were exsanguinated, examined for gross pathology, and tissues preserved for histopathology. There were no deaths caused by holo-rhLF and in-life physical signs were generally normal. Although statistical differences were noted in some hematology, clinical chemistry and heart/body weight ratios, they were of questionable biological significance. A significantly greater total iron binding capacity (TIBC) was detected in the blood of male animals dosed with holo-rhLF. Serum was analyzed for the presence of IgG and IgE antibodies; demonstrating low levels of IgG antibodies to the human protein, but no increase in IgE antibodies. There was no increase in serum lactoferrin levels. The results of the 28-day oral administration demonstrate a lack of toxicity of holo-rhLF in rats. There were no treatment related, toxicologically relevant changes in clinical signs, growth, food consumption, hematology, clinical chemistry, organ weights or pathology. The no observed adverse effect level (NOAEL) is greater than 1000 mg/kg/day.

Topics: Administration, Oral; Animals; Body Weight; Dose-Response Relationship, Drug; Eating; Female; Humans; Immunoglobulin E; Immunoglobulin G; Iron; Lactoferrin; Male; No-Observed-Adverse-Effect Level; Organ Size; Oryza; Rats; Rats, Wistar; Sex Factors; Toxicity Tests

The human Enterovirus genus of the piconavirus family causes most of the febrile illnesses that affect children during the summer season in Taiwan. Enterovirus type 71 (EV71) plays a key role in patients with hand-foot-and-mouth disease (HFMD) combined with severe paralysis or encephalitis. It is important to find a method for preventing infection with EV71 since there is no antiviral agent or vaccine for humans. In this study, we developed a transgenic mouse model for demonstrating the protective effects of recombinant lactoferrin (LF) against EV71 infection. Transgenic mice carrying alpha-lactalbumin-porcine lactoferrin (alphaLA-pLF) and BALB/c wild-type mice were subjected to EV71 inoculation. First, we analyzed the expression efficiencies of recombinant pLF (rpLF) in hemizygous and homozygous transgenic mice. Following EV71 inoculation on the 4th day of life, pups ingesting transgenic milk showed the significantly higher survival rate and heavier body weight compared to wild-type mice. RT-PCR analysis for EV71 viral RNA showed that the recombinant pLF had a blocking effect on EV71 infection. Our data suggest that oral intake of pLF-enriched milk exhibited the ability to prevent infection with EV71. The study also provides an animal model for validating the protective effects of pLF.

Topics: Animals; Animals, Newborn; Antiviral Agents; Body Weight; Child, Preschool; Disease Models, Animal; Enterovirus; Enterovirus Infections; Female; Humans; Infant, Newborn; Lactalbumin; Lactation; Lactoferrin; Mice; Mice, Inbred BALB C; Mice, Transgenic; Milk; Recombinant Proteins; Swine

We investigated the effects of bovine LF (bLF) on different phases of NNK-induced lung tumorigenesis in A/J mice. Mice were orally administered 0.02, 0.2 and 2% bLF during the initiation phase, and 2% bLF during the whole tumorigenesis phase or post-initiation phase. Administered bLF during the post-initiation phase showed significant reduction of macroscopical lung nodules, and immunohistochemically decreased expression levels of cell proliferation marker and increased expression levels of apoptosis marker in lung proliferative lesions. bLF might inhibit NNK-induced mouse lung tumorigenesis, only when given limited to the post-initiation phase, through modification of cell proliferation and/or apoptosis.

Topics: Adenoma; Animals; Body Weight; Caspase 3; Cattle; Dietary Supplements; Female; Hyperplasia; Lactoferrin; Lung; Lung Neoplasms; Mice; Mice, Inbred A; Nitrosamines; Organ Size; Proliferating Cell Nuclear Antigen

The European Commission has proposed a permanent ban on the use of antibiotics as an ingredient in animal feed to promote growth. Lactoferrin is a globular multifunctional protein that has been shown to play a role in iron absorption and to have antimicrobial and anti-inflammatory activities. Therefore, lactoferrin may serve as a nontherapeutic alternative to antibiotics in livestock husbandry. As a pilot study toward this goal, transgenic mice have been generated harboring a porcine lactoferrin (pLF) gene driven by the mammary gland-specific promoter of the bovine alpha-lactalbumin (alphaLA) gene. The alphaLA-pLF hybrid gene was confirmed to have been successfully integrated and transmitted stably through the germ-line in 9 (5 females and 4 males) of 14 transgenic founders. In the female progenies of six lines analyzed, the transgene copy numbers ranged from 1 to 20 with 1-4 integration sites. Significant levels of pLF protein in milk ranging from 40 to 106 microg/mL with physical characteristics similar to those of native pLF in sow's milk were achieved in three of the transgenic lines obtained. Tissue- and stage-specific pLF expressions were restricted to the mammary gland of the transgenic female mice during lactation. It was further demonstrated that the growth performance of animal pups is enhanced by directly feeding the genetically engineered milk containing enriched pLF protein in transgenic mice. Furthermore, this enhanced growth performance in suckling mice was proportional to the concentration of pLF present in milk.

Topics: Animals; Base Sequence; Body Weight; Cattle; Duodenum; Female; Food, Genetically Modified; Intestinal Mucosa; Lactalbumin; Lactation; Lactoferrin; Mice; Mice, Transgenic; Microvilli; Milk; Molecular Sequence Data; Polymerase Chain Reaction; Promoter Regions, Genetic; Swine; Weight Gain

A total of 90 weanling female pigs (Duroc x Landrace x Yorkshire) were used in a 30-d growth experiment to investigate the effect of lactoferrin (LF) on growth performance, immune function, and serum iron concentrations. The pigs were allocated on the basis of BW and litter to 3 dietary treatments in a randomized complete block design. The dietary treatments were: control group (basal diet), antibiotics group (basal diet + 20 mg/kg of flavomycin + 110 mg/kg of aureomycin), and LF group (basal diet + 1.0 g/kg of LF). There were 3 replicate pens per treatment, and pigs were grouped with 10 pigs per pen. Six pigs, randomly selected from each treatment (2 pigs/pen), were slaughtered for serum and spleen samples on d 15 and 30. Supplementation with LF improved the phytohemagglutinin (PHA)-stimulated peripheral lymphocyte proliferation by 36% (P < 0.01), increased concanavalin A (ConA)- and PHA-induced spleen lymphocyte proliferation by 332% (P < 0.01) and 258% (P < 0.01), enhanced serum IgG by 20% (P < 0.05), IgA by 13% (P < 0.05), IgM by 15% (P < 0.05), complement 4 (C4) by 29% (P < 0.05), IL-2 by 12% (P < 0.01), and serum iron values by 22% (P < 0.05) on d 15 compared with the control. Lactoferrin supplementation increased PHA-stimulated lymphocyte proliferation (P < 0.01), serum IgG by 16% (P < 0.05), IgA by 17% (P < 0.05), C4 by 11% (P < 0.05), IL-2 by 14% (P < 0.05), and serum iron values by 23% (P < 0.01), and decreased the diarrhea ratio (P < 0.05) relative to the control on d 30. Compared with the controls, supplementation with antibiotic increased ConA- and PHA-induced spleen lymphocyte proliferation (P < 0.05) on d 15, decreased the diarrhea ratio (P < 0.05), and increased the PHA-induced spleen lymphocyte proliferation (P < 0.05) and serum iron values (P < 0.01) on d 30. These results support the possible use LF as an immunostimulant to improve immune functions and strengthen host defenses and would seem to be a good method for defending weanling piglets from infections and weanling stress.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Anti-Bacterial Agents; Body Weight; Cell Proliferation; Cytokines; Diarrhea; Female; Immunoglobulins; Iron; Lactoferrin; Lymphocyte Activation; Lymphocytes; Random Allocation; Spleen; Swine; Swine Diseases; Weaning; Weight Gain

Rates of protein synthesis (PS) and turnover are more rapid during the neonatal period than during any other stage of postnatal life. Vitamin A and lactoferrin (Lf) can stimulate PS in neonates. However, newborn calves are vitamin A deficient and have a low Lf status, but plasma vitamin A and Lf levels increase rapidly after ingestion of colostrum. Neonatal calves (n = 6 per group) were fed colostrum or a milk-based formula without or with vitamin A, Lf, or vitamin A plus Lf to study PS in the jejunum and liver. l-[(13)C]Valine was intravenously administered to determine isotopic enrichment of free (nonprotein-bound) Val (AP(Free)) in the protein precursor pool, atom percentage excess (APE) of protein-bound Val, fractional protein synthesis rate (FSR) in the jejunum and liver, and isotopic enrichment of Val in plasma (APE(Pla)) and in the CO(2) of exhaled air (APE(Ex)). The APE, AP(Free), and FSR in the jejunum and liver did not differ significantly among groups. The APE(Ex) increased, whereas APE(Pla) decreased over time, but there were no group differences. Correlations were calculated between FSR(Jej) and histomorphometrical and histochemical data of the jejunum, and between FSR(Liv) and blood metabolites. There were negative correlations between FSR(Liv) and plasma albumin concentrations and between FSR(Jej) and the ratio of villus height:crypt depth, and there was a positive correlation between FSR(Jej) and small intestinal cell proliferation in crypts. Hence, there were no effects of vitamin A and Lf and no interactions between vitamin A and Lf on intestinal and hepatic PS. However, FSR(Jej) was correlated with histomorphometrical traits of the jejunum and FSR(Liv) was correlated with plasma albumin concentrations.

Topics: Animals; Animals, Newborn; Blood Proteins; Body Temperature; Body Weight; Breath Tests; Carbon Isotopes; Cattle; Colostrum; Diet; Health Status; Immunoglobulins; Jejunum; Kinetics; Lactoferrin; Liver; Male; Organ Size; Protein Biosynthesis; Serum Albumin, Bovine; Urea; Valine; Vitamin A

Cyclophosphamide (CP) is used in the treatment of autoimmune disorders and leukemia. The compound induces severe leuko- and neutropenia. Lactoferrin (LF) is a protein which plays a role in the innate immunity. In this study we evaluated the usefulness of LF in reversing CP-induced lympho- and neutropenia in mice.. CBA mice were treated with CP (350 mg/kg body weight, intraperitoneally) and given LF as a 0.5% addition to drinking water. Alternatively, LF was administered orally (seven doses, 1 mg each) on alternate days following CP injection. Control groups received CP or LF only. Blood samples were taken before treatment and on days 4, 8, 15 and 22 following CP injection to determine leukocytosis and cell types in blood smears.. Mice treated with CP showed severe leukopenia, strong eosinophilia (day 4), and an altered lymphocyte/neutrophil ratio (days 8-22). Treatment of mice with LF for 21 days partially normalized the cell composition in CP-treated mice (increased percentage of lymphocytes and decreased eosinophil content). The content of leukocytes increased upon LF treatment on days 4, 8, 15 and 22 (by 36.8, 39.5, 72 and 70.7%, respectively). More importantly, LF partly normalized the neutrophil and lymphocyte composition on day 22 (neutrophils: 29.2% in control mice, 50.6% in CP-treated, and 39.16% in CP/LF-treated; lymphocytes: 66.18% in control mice, 35% in CP-treated and 48.8% in CP/LF-treated). Administration of LF alone did not change the cell numbers or composition.. LF given orally to CP-immunocompromised mice accelerates reconstitution of lymphopoiesis and myleopoiesis.

Topics: Animals; Body Weight; Cyclophosphamide; Eosinophils; Immunosuppressive Agents; Lactoferrin; Leukocytosis; Lymphocytes; Lymphopenia; Mice; Mice, Inbred CBA; Myelopoiesis; Neutropenia; Neutrophils; Time Factors

Topics: Animals; Body Weight; Cholesterol; Clinical Trials as Topic; Humans; Intestinal Absorption; Lactoferrin; Tablets, Enteric-Coated; Triglycerides

The modifying effects of dietary feeding of bovine lactoferrin (bLF) on tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. The activities of phase II detoxifying enzymes, glutathione S-transferase (GST) and quinone reductase (QR), polyamine content and ornithine decarboxylase (ODC) activity in the tongue were also examined for mechanistic analysis of possible modifying effects of bLF on carcinogenesis. At 7 weeks of age, all animals except those treated with bLF alone and untreated rats were given 20 ppm 4-NQO in drinking water for 8 weeks to induce tongue neoplasms. Starting 7 days before 4-NQO exposure, experimental groups were fed experimental diets containing bLF (0.2% and 2%) for 10 weeks ("initiation feeding"). Starting 1 week after the cessation of exposure to 4-NQO, the other experimental groups given 4-NQO and a basal diet were fed the experimental diets for 22 weeks ("postinitiation feeding"). At week 32, the incidence and multiplicity of tongue neoplasms in the "initiation feeding" groups of 0.2% and 2% bLF and the "post-initiation feeding" group of 0.2% bLF were lower than those of the 4-NQO alone group, but without statistical significance. However, "post-initiation feeding" of 2% bLF caused a significant reduction in the incidence (20% vs. 55%, P=0.02418) and multiplicity (0.25+/-0.54 vs. 0.70+/-0.71, P<0.05) of tongue squamous cell carcinoma (by 64%, P=0.02418). bLF treatment elevated liver and tongue GST activities and liver QR activity. The "post-initiation feeding" with 2% bLF significantly decreased QR activity, proliferating cell nulcear antigen-positive index and ODC activity in the tongue. In addition, feeding with bLF decreased tongue polyamine content. These results suggest that bLF, when given at the 2% dose level during the post-initiation phase, exerts chemopreventive action against tongue tumorigenesis through modification of cell proliferation activity and/or the activities of detoxifying enzymes.

Topics: 4-Nitroquinoline-1-oxide; Animals; Body Weight; Carcinogens; Cattle; Epithelium; Glutathione Transferase; Immunohistochemistry; Lactoferrin; Liver; Male; Mucous Membrane; NAD(P)H Dehydrogenase (Quinone); Organ Size; Ornithine Decarboxylase; Precancerous Conditions; Proliferating Cell Nuclear Antigen; Quinolones; Rats; Rats, Inbred F344; Tongue; Tongue Neoplasms

Bovine lactoferrin (LF), which is an iron-binding glycoprotein in milk, was administered orally to groups of 12 males and 12 female rats at dose levels of 200, 600 and 2000mg/kg/day once daily for 13 weeks and its toxicity on repeated administration was examined. Throughout the administration period, there were no deaths caused by administration of the test compound, nor were there any adverse effects noted in the general condition of the animals. The study findings concerning body weight and food consumption, ophthalmology, urinalysis including water consumption, haematology, blood chemistry, necropsy, organ weights and histopathology revealed that there were no apparent changes due to administration of LF. Therefore, the level of LF at which no adverse effect was observed was considered to be 2000mg/kg/day for both sexes.

Topics: Administration, Oral; Animals; Anti-Infective Agents; Body Weight; Cattle; Eating; Female; Lactoferrin; Male; Rats; Rats, Sprague-Dawley

Chemopreventive effects of bovine lactoferrin (bLF), which is found at high concentrations in colostrum, on rat bladder carcinogenesis were investigated using a rat bladder medium-term bioassay. In experiment 1, a total of 80 F344 male rats, 6 weeks old, were divided into 5 groups. Groups 1 and 2 were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 8 weeks and after a 1-week interval, received dietary supplementation with 2% and 0.2% bLF, respectively. Group 3 received 0.05% BBN for 8 weeks and then no treatment. Group 4 was administered 2% bLF alone from week 9, without prior carcinogen exposure. Group 5 was maintained without any treatment throughout the experiment. All rats were killed at the end of week 36. Group 1 demonstrated a significantly decreased multiplicity of the bladder tumors (carcinomas and papillomas) as compared with group 3. Maximum cut surface areas of bladder tumors were also significantly decreased in groups 1 and 2 compared with group 3. No bladder tumors were observed in groups 4 or 5. In experiment 2, a total of 60 rats were divided into two groups (30 rats each); both were treated with 0.05% BBN for 4 weeks and after a 1-week interval, one received 2% bLF (group 1) and the other, basal diet (group 2) for 4 weeks. Group 1 demonstrated a tendency for decrease of the 5-bromo-2'-deoxyuridine (BrdU) labeling index. bLF was detected in the urine of rats fed bLF by ELISA as well as western blot analysis. The findings indicate that 2% bLF can inhibit BBN-induced rat bladder carcinogenesis, and that this may be due to bLF in the urine.

Topics: Acetyltransferases; Animals; Anticarcinogenic Agents; Body Weight; Butylhydroxybutylnitrosamine; Carcinogens; Cattle; Chlorides; Drinking; Eating; Hydrogen-Ion Concentration; Lactoferrin; Liver; Male; Mucous Membrane; Organ Size; Ornithine Decarboxylase; Potassium; Rats; Rats, Inbred F344; Sodium; Urinary Bladder; Urinary Bladder Neoplasms

Recombinant human lactoferrin possesses in-vitro antibiotic and anti-inflammatory activity similar to the native form. It was tested for in-vivo activity in mice infected with the gastritis-inducing bacterium Helicobacter felis. A two-week course of treatment with lactoferrin was sufficient to partially reverse both infection-induced gastritis and the infection rate, and fully reverse gastric surface hydrophobicity changes. A comparison of lactoferrin with amoxicillin and standard triple therapy revealed no differences in infection rate. These results show that recombinant human lactoferrin is effective in a mouse model of Helicobacter infection, and support further testing of this promising agent for this application.

Topics: Amoxicillin; Animals; Body Weight; Dose-Response Relationship, Drug; Gastritis; Helicobacter; Helicobacter Infections; Humans; Lactoferrin; Mice; Mice, Inbred C57BL; Organ Size; Penicillins; Recombinant Proteins; Stomach; Time Factors

A milk component, bovine lactoferrin (bLF), previously shown by us to be a strong chemopreventive of colon carcinoma development, was examined for its influence on other organs using a rat multi-organ carcinogenesis model. Male F344 rats, aged 6 weeks, were treated sequentially with diethylnitrosamine (DEN, i.p.), dihydroxy-di-N-propylnitrosamine (DHPN, in drinking water) and N-nitrosomethylbenzylamine (NMBA, s.c.) during the first 8 weeks (DDN treatment), and then bLF was administered in the basal diet, at a dose of 2, 0.2, 0.02 or 0.002%. Other groups were given DDN treatment or bLF alone as controls. All surviving animals were killed at week 41, and major organs were examined histopathologically for neoplastic lesions. In the esophagus, a tendency for reduction in development of papillomas was evident in the bLF-treated animals, along with a significant suppression of relatively large-sized papillomas (more than 50 mm3 volume) at the 0.2% dose (P<0.05, 11% of the control). The multiplicity of tumors (adenomas and carcinomas) in the lung was also decreased in animals fed 0.02% bLF (1.98+/-0.41 per cm2 lung tissue section, P<0.05) compared to the control group (3.48+/-0.33). No enhancing or inhibitory effects of bLF on tumor development in other organs were noted. The present results indicate that bLF exerts chemopreventive effects in the esophagus and lung in addition to the colon.

Topics: Adenoma; Animals; Anticarcinogenic Agents; Body Weight; Carcinogens; Carcinoma; Cattle; Dose-Response Relationship, Drug; Esophageal Neoplasms; Incidence; Lactoferrin; Lung Neoplasms; Male; Organ Size; Papilloma; Rats; Rats, Inbred F344; Survival Rate

Isoproterenol hydrochloride (ISO), a beta adrenergic agonist, is known to cause ischemic necrosis in rats. Cardiotoxicity of three different doses of ISO were studied using physiological, biochemical and histopathological parameters. The effects of single and double dose of ISO were analysed, which illustrated that single ISO dose was more cardiotoxic than double ISO dose due to ischemic preconditioning. The tetrapeptide derivatives L-lysine-L-arginine-L-aspartic acid-L-serine (tetrapeptide A) and di-tert.butyloxycarbonyl-L-lysine-L-arginine-L-aspartic acid-tert.butyl O-tert.butyl-L-serinate (tetrapeptide B) along with acetylsalicylic acid as positive control were analysed at different time points for their cardioprotective effect. The results demonstrated that optimal protective effects were observed by pretreatment with 5 mg/kg of tetrapeptide B and this was found to be slightly better than that of acetylsalicylic acid. A lesser degree of cardioprotection was noticed when low doses of tetrapeptide B were administered. This study clearly showed that single dose of ISO (50 mg/kg, s.c.) induced myocardial necrosis could be used as a model to assess cardiovascular drugs and in this model, it was demonstrated that the tetrapeptide B could exhibit optimal cardioprotective effect.

Topics: Adrenergic beta-Agonists; Animals; Aspirin; Body Weight; Creatine Kinase; Disease Models, Animal; Female; Hemodynamics; Hemorrhage; Isoproterenol; L-Lactate Dehydrogenase; Lactoferrin; Myocardial Ischemia; Myocardium; Necrosis; Oligopeptides; Organ Size; Peptide Fragments; Platelet Aggregation Inhibitors; Rats; Rats, Wistar

The clinical efficacy of a preparation based on the lactoperoxidase system (LP-s) and lactoferrin (LF) was tested in calves experimentally infected with E coli K99+, Ent+. Mortality, occurrence and duration of diarrhoea were significantly lower (P less than 0.05) and general clinical status significantly better (P less than 0.05) in infected calves treated with LP-s and LF preparation than in infected but non-treated calves. Results suggest that LP-s and lactoferrin are effective in the treatment of enteric colibacillosis in calves.

Topics: Animals; Body Weight; Cattle; Cattle Diseases; Diarrhea; Drug Therapy, Combination; Escherichia coli Infections; Feces; Glucose; Glucose Oxidase; Lactoferrin; Lactoglobulins; Lactoperoxidase; Peroxidases; Random Allocation; Thiocyanates

Lactoferrin was measured in breast milk from Aboriginal and non-Aboriginal Australian women using an enzyme immunoassay. There was no diurnal variation in lactoferrin concentration or change in concentration between the beginning and end of a feed. Lactoferrin levels were significantly higher in the first 15 days postpartum than in the period after the 15th day. Regression analysis showed that in milk from Aboriginal women less than 15 days postpartum, higher concentrations of lactoferrin were associated with weight for height (WFH) greater than 90% and with increased parity. Comparable data were not available for Caucasian women. For Aboriginal and Caucasian women more than 15 days postpartum, lactoferrin concentrations were higher in women greater than 90% WFH. Other variables, such as parity, were not significant in the regression.

Topics: Adult; Body Height; Body Weight; Circadian Rhythm; Female; Humans; Immunoenzyme Techniques; Lactoferrin; Lactoglobulins; Milk, Human; Native Hawaiian or Other Pacific Islander; Nutritional Physiological Phenomena; Postpartum Period; Pregnancy; Time Factors