Administration Of Lactoferrin Research Articles

Assessment of single and combined administration of ubiquinone and lactoferrin on histopathology, ultrastructure, oxidative stress, and WNT4 expression gene induced by thioacetamide on hepatorenal system of adult male rats

BackgroundHepatorenal syndrome is a life-threatening medical complication of liver cirrhosis. Hepatic cirrhosis is commonly accompanied by rapid failure of renal functions. Thioacetamide (TAA) is a potent hepatotoxin and a class 2-type carcinogen. Ubiquinone (Coq10) and lactoferrin (LF) are potent antioxidants with antifibrotic and antiinflammatory effects. However, whether Coq10 and LF reduce the hepatorenal injury induced by TAA remains unclear. Here, we investigated the potential protective effect of both/or Coq10 and LF in ameliorating TAA-induced hepatorenal injury and the role of WNT4 gene expression in detecting TAA-induced renal injury in rats. Seventy healthy and mature male Sprague Dawley rats, weighting (200 g ± 20 g) and aging (4–6) weeks were randomly divided into seven groups (n = 10): control, Coq10, LF, TAA, TAA + Coq10, TAA + LF, and TAA + Coq10 + LF. The hepatorenal injury was induced through intraperitoneal (i.p.) injection of TAA (150 mg/kg/twice/weekly) for nine weeks. Coq10 (10 mg/kg/day) and LF (200 mg/kg/day) were orally administered for nine weeks.ResultsTAA induced marked hepatorenal damage, evident by the significant increase in the alanine aminotransferase (ALT), aspartate transaminase (AST), serum creatinine (SCr) activities, and the blood urea nitrogen (BUN) level. Besides, the significant increases in concentrations of malondialdehyde (MDA) and nitric oxide (NOx) together with significant decreases in the activities of catalase (CAT) and superoxide dismutase (SOD). The histopathological analysis of the TAA group showed obvious fibrosis, steatosis, and inflammation of the hepatic parenchyma as well as severe glomerular and tubular damage of the renal parenchyma. In addition, TAA induced marked ultrastructural alterations and up-regulation in the expression of the WNT4 gene in the kidney. Meanwhile, the biochemical, histopathological, and ultrastructural alterations were significantly decreased with significant down-regulation in the expression of WNT4 in the groups exposed to TAA and treated with Coq10 and LF.ConclusionOur data suggested that Coq10 and LF could have protective effects on TAA hepatorenal damage, through improving the hepatic and renal functions, reduction of oxidative stress, structural and ultrastructural alterations, besides down-regulation in the expression of WNT4.

Lactoferrin Has a Protective Effect on Mouse Brain Cells after Acute Gamma Irradiation of the Head.

We studied the effect of human lactoferrin on cells of the hippocampal dentate gyrus of 2-2.5-month-old male C57BL/6 mice after acute gamma irradiation of the head in a dose of 8 Gy from a 60Co source. Immediately after irradiation some animals received an intraperitoneal injection of human lactoferrin (4 mg/mouse). The appearance of TUNEL+ cells in the subgranular zone 6 h after irradiation was accompanied by a corresponding decrease in the number of Ki-67- and DCX-immunoreactive cells. Administration of lactoferrin had a protective effect on mouse brain cells, which manifested in a decrease in the number of TUNEL+ cells (by 77% relative to the irradiation alone) and an increase in the number of proliferating cells (from 16 to 61% relative to control animals) and immature neurons (from 14 to 22% relative to control animals) in the dentate gyrus of the hippocampus.

Lactoferrin ameliorates carfilzomib-induced renal and pulmonary deficits: Insights to the inflammasome NLRP3/NF-κB and PI3K/Akt/GSK-3β/MAPK axes

AimsCarfilzomib, an irreversible proteasome inhibitor, has been increasingly used to treat multiple myeloma worldwide. However, case studies showed its treatment has been associated with cardiac, renal, and pulmonary deleterious effects. Lactoferrin is an iron-binding glycoprotein present in milk. It is a multifunctional protein with antimicrobial activity, antitumor, antioxidant, and anti-inflammatory effects. Thus, this study aimed to assess the protective effects of lactoferrin against carfilzomib-induced nephrotoxicity and pulmonary toxicity, in addition to identifying the possible underlying molecular mechanisms. Main methodsMice were treated with lactoferrin (300 mg/kg/day) concomitantly with carfilzomib (4 mg/kg, i.p.) twice weekly for three weeks. Kidney and lung indices, serum creatinine, blood urea nitrogen (BUN), uric acid, kidney injury molecule-1 (KIM-1), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and histological examination were assessed. In addition, biochemical analyses of the inflammasome NLRP3/NF-κB and PI3K/Akt/GSK-3β/MAPK axes were conducted. Key findingsTreatment with lactoferrin decreased serum levels of creatinine, BUN, uric acid, KIM-1, ALP, AST, and LDH and reversed carfilzomib-induced histological changes in both kidney and lung. The inflammatory markers NLRP3, p65 NF-kB, caspases1, interleukin-1β, and interleukin-18, as well as the MAPK signaling pathway, were significantly reduced in renal and pulmonary tissues of mice following lactoferrin administration. Moreover, lactoferrin significantly counteracted carfilzomib-induced reduced expression of pAkt and pGSK-3β in both renal and pulmonary tissues. SignificanceThe current study suggests lactoferrin might be a promising candidate for ameliorating carfilzomib-induced nephrotoxicity and pulmonary toxicity.

Effect of oral administration of bovine lactoferrin on the pulmonary immune response in a mouse model of restraint stress

Effect of oral administration of bovine lactoferrin on the pulmonary immune response in a mouse model of restraint stress

Oral lactoferrin administration does not impact the diversity or composition of the infant gut microbiota in a Peruvian cohort.

Lactoferrin is a protein from breast milk involved in early-life microbiome assembly. It is believed to promote the growth of lactic acid-producing bacteria and inhibit pathogens by limiting iron availability and enabling an acidic environment in the gut. Previous reports suggest that oral administration of lactoferrin in neonates promotes the increase of gut microbiota diversity and the enrichment of beneficial microbes. However, its effect on infant gut microbiota over time has yet to be thoroughly studied to fully understand its potential as a prebiotic. Using 16s rRNA gene amplicon sequencing, we analyzed the gut microbiota composition of 60 toddlers at 12-18 months of age from Lima, Peru, who received daily oral administration of lactoferrin or placebo for 6 months since enrollment. Samples were analyzed at 0, 2, and 4 months after beginning treatment. Our results show that lactoferrin treatment does not increase gut microbiota diversity over time nor affect its bacterial composition compared to the placebo group.IMPORTANCEPrevious studies have suggested that oral lactoferrin enhances diversity in the gut microbiota in infants while inhibiting the growth of opportunistic pathogens. However, the effect of lactoferrin on infant gut microbiota over time has yet to be thoroughly studied. Our study suggests that lactoferrin oral treatment in infants aged 12-18 months does not affect gut microbiome diversity and composition over time. To our knowledge, this is the first study to report the effect of lactoferrin on infant gut microbiome composition over time and helps elucidate its impact on infant health and its therapeutic potential.

Early Neuroprotective Effects of Bovine Lactoferrin Associated with Hypothermia after Neonatal Brain Hypoxia-Ischemia in Rats.

Neonatal hypoxic-ischemic (HI) encephalopathy (HIE) in term newborns is a leading cause of mortality and chronic disability. Hypothermia (HT) is the only clinically available therapeutic intervention; however, its neuroprotective effects are limited. Lactoferrin (LF) is the major whey protein in milk presenting iron-binding, anti-inflammatory and anti-apoptotic properties and has been shown to protect very immature brains against HI damage. We hypothesized that combining early oral administration of LF with whole body hypothermia could enhance neuroprotection in a HIE rat model. Pregnant Wistar rats were fed an LF-supplemented diet (1 mg/kg) or a control diet from (P6). At P7, the male and female pups had the right common carotid artery occluded followed by hypoxia (8% O2 for 60') (HI). Immediately after hypoxia, hypothermia (target temperature of 32.5-33.5 °C) was performed (5 h duration) using Criticool®. The animals were divided according to diet, injury and thermal condition. At P8 (24 h after HI), the brain neurochemical profile was assessed using magnetic resonance spectroscopy (1H-MRS) and a hyperintense T2W signal was used to measure the brain lesions. The mRNA levels of the genes related to glutamatergic excitotoxicity, energy metabolism and inflammation were assessed in the right hippocampus. The cell markers and apoptosis expression were assessed using immunofluorescence in the right hippocampus. HI decreased the energy metabolites and increased lactate. The neuronal-astrocytic coupling impairments observed in the HI groups were reversed mainly by HT. LF had an important effect on astrocyte function, decreasing the levels of the genes related to glutamatergic excitotoxicity and restoring the mRNA levels of the genes related to metabolic support. When combined, LF and HT presented a synergistic effect and prevented lactate accumulation, decreased inflammation and reduced brain damage, pointing out the benefits of combining these therapies. Overall, we showed that through distinct mechanisms lactoferrin can enhance neuroprotection induced by HT following neonatal brain hypoxia-ischemia.

Lactoferrin for the postoperative management of term neonates after gastrointestinal surgery.

Neonates who have undergone gastrointestinal surgery are particularly susceptible to infectious complications in the postoperative period. This may be due in part to disruption of the integrity of the gut and its altered intestinal microflora. Lactoferrin is a whey protein found in milk and is an important innate mammalian defence mechanism. Lactoferrin has been reported to have antimicrobial and anti-inflammatory properties. It has also been reported to help establish a healthy gut microflora and aid in the intestinal immune system. Lactoferrin supplementation has been reported to decrease sepsis in preterm infants. There may be a role for lactoferrin to reduce the incidence of sepsis, thus reducing morbidity and mortality and improving enteral feeding in postoperative term neonates. The primary objective of this review was to evaluate the efficacy of administering lactoferrin on the incidence of sepsis and mortality in term neonates after gastrointestinal surgery. The secondary objective was to assess the impact of administering lactoferrin on time to full enteral feeds, the intestinal microflora, duration of hospital stay, and mortality before discharge in the same population. The Cochrane Neonatal Information Specialist searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase Ovid, CINAHL, the WHO ICTRP and ClinicalTrials.gov trials registries. The date of the last search was February 2023. There were no restrictions to language, publication year or publication type. We checked references of potentially relevant studies and systematic reviews. We planned to include randomised controlled trials that studied infants born at 37 or more weeks of gestation who had one or more episodes of gastrointestinal surgery within 28 days of birth, and compared administration of lactoferrin with a placebo. We used standard Cochrane methodological procedures. We planned to use the GRADE approach to assess the certainty of evidence for each outcome. We identified no published randomised controlled studies that assessed the efficacy of lactoferrin for the postoperative management of term neonates following gastrointestinal surgery. There is currently no evidence available from randomised controlled trials to show whether lactoferrin is effective or ineffective for the postoperative management of term neonates after gastrointestinal surgery. There is a need for randomised controlled trials to be performed to assess the role of lactoferrin in this setting.

Role of the protein kinase A signaling pathway and identification of mediators in the cardioprotective effects of enteral lactoferrin for ischemia-reperfusion injury in an isolated rat heart model

ObjectiveLactoferrin is an iron-binding glycoprotein. Enteral lactoferrin attenuates myocardial ischemia-reperfusion (IR) injury, but the underlying mechanism remains unknown. The aim of this study was to investigate protein kinase A (PKA) signaling pathway activation and levels of serum glucagonlike peptide-1 (GLP-1), secreted by intestinal endocrine L cells, and adiponectin, secreted by adipose tissue, after enteral lactoferrin administration. MethodsHearts (N = 32) were excised from Wistar rats and perfused using a Langendorff system. To assess the role of the PKA pathway in the cardioprotective effects of lactoferrin, an inhibitor of PKA (H89) was applied before no-flow ischemia. Rats were randomly divided into four groups: control, lactoferrin (LF), control+H89, and LF+H89. The control and control+H89 groups were administered normal saline by gavage, and the LF and L +H89 groups were administered bovine lactoferrin (1000 mg/kg) by gavage 15 min before intraperitoneal pentobarbital injection. Muscle sampling was performed at the end of reperfusion. When rats were sacrificed, blood was sampled to measure hormone levels. The primary outcome was maximum left ventricular pressure derivative (LV dP/dt max) 15 min after reperfusion. ResultsLV dP/dt max at 10 and 15 min after reperfusion was significantly higher in the LF group than in the control group (P < 0.05), and the effect was diminished by H89. The PKA pathway was significantly activated in the LF group. Enteral lactoferrin increased serum GLP-1 but not serum adiponectin levels. ConclusionsEnteral lactoferrin induces cardioprotective effects against myocardial IR injury via the PKA signaling pathway and increases serum GLP-1 levels.

Lactoferrin/sialic acid prevents adverse effects of intrauterine growth restriction on neurite length: investigations in an in vitro rabbit neurosphere model.

Intrauterine growth restriction (IUGR) is a well-known cause of impaired neurodevelopment during life. In this study, we aimed to characterize alterations in neuronal development underlying IUGR and discover strategies to ameliorate adverse neurodevelopment effects by using a recently established rabbit in vitro neurosphere culture. IUGR was surgically induced in pregnant rabbits by ligation of placental vessels in one uterine horn, while the contralateral horn remained unaffected for normal growth (control). At this time point, rabbits were randomly assigned to receive either no treatment, docosahexaenoic acid (DHA), melatonin (MEL), or lactoferrin (LF) until c-section. Neurospheres consisting of neural progenitor cells were obtained from control and IUGR pup's whole brain and comparatively analyzed for the ability to differentiate into neurons, extend neurite length, and form dendritic branching or pre-synapses. We established for the very first time a protocol to cultivate control and IUGR rabbit neurospheres not only for 5 days but under long-term conditions up to 14 days under differentiation conditions. Additionally, an in vitro evaluation of these therapies was evaluated by exposing neurospheres from non-treated rabbits to DHA, MEL, and SA (sialic acid, which is the major lactoferrin compound) and by assessing the ability to differentiate neurons, extend neurite length, and form dendritic branching or pre-synapses. We revealed that IUGR significantly increased the neurite length after 5 days of cultivation in vitro, a result in good agreement with previous in vivo findings in IUGR rabbits presenting more complex dendritic arborization of neurons in the frontal cortex. MEL, DHA, and SA decreased the IUGR-induced length of primary dendrites in vitro, however, only SA was able to reduce the total neurite length to control level in IUGR neurospheres. After prenatal in vivo administration of SAs parent compound LF with subsequent evaluation in vitro, LF was able to prevent abnormal neurite extension. We established for the first time the maintenance of the rabbit neurosphere culture for 14 days under differentiation conditions with increasing complexity of neuronal length and branching up to pre-synaptic formation. From the therapies tested, LF or its major compound, SA, prevents abnormal neurite extension and was therefore identified as the most promising therapy against IUGR-induced changes in neuronal development.

Lactoferrin Influence on the Course of Suppurative Corneal Ulcer

Research justification. Corneal ulcer is a common corneal pathology dangerous because of its complications, which occur in 2.5–37.9 % of cases despite modern treatment. Thus, the development of novel methods improving the results of corneal ulcer treatment is very important.Research objective was to evaluate the efficacy of lactoferrin-based therapy for experimental suppurative corneal ulcer.Material and methods. The study was performed in male chinchilla rabbits. Three intact rabbits (6 eyes) were used as control animals. Staphylococcus suppurative corneal ulcer was modeled in both eyes of 63 experimental animals. These rabbits were randomized into three groups. The first group was administered placebo therapy, the second group received antibacterial therapy, and the third group — instillations of lactoferrin. The area of ulcerative lesion was used as the measure of the therapeutic efficacy of the treatment. Then, a histological study was performed, and microsamples were photographed with LOMO TC-500 digital camera (Russia).Results. Lactoferrin instillations resulted in reliable increase in the number of transfers from infiltration stage to epithelization stage, decrease in the percentage of ulcerations, and in the proportion of critical thinning of the cornea, as well as decrease in the proportion of perforations. However, it was noticed that lactoferrin treatment when continued after the end of epithelization process resulted in excessive formation of opaque scar tissue.Conclusion. Local administration of lactoferrin stimulates the epithelium regeneration and the formation of the connective tissue and thus prevents the development of complications of suppurative corneal ulcer. However, the identified excessive formation of opaque scar tissue in lactoferrin treatment lasting too long has to be taken into consideration when developing the optimal scheme for lactoferrin treatment.

The mechanism underlying the remodeling effect of lactoferrin on midpalatal sutures during maxillary expansion and relapse in rats

The remodeling effects of intragastric administration and intramaxillary injection of lactoferrin (LF) on midpalatal sutures (MPS) during maxillary expansion and relapse in rats were studied to explore the underlying bone remodeling mechanism. Using a rat model of maxillary expansion and relapse, rats were treated with LF by intragastric administration (1 g·kg-1·d-1) or intramaxillary injection (5 mg·25 μl-1·d-1). The effects of LF on the osteogenic and osteoclast activities of MPS were observed by microcomputed tomography, histologic staining, and immunohistochemical staining, and the expressions of key factors in the extracellular regulated protein kinase 1/2 (ERK1/2) pathway and osteoprotegerin (OPG)-receptor activator of nuclear factor-KB ligand (RANKL)-receptor activator of nuclear factor-KB (RANK) axis were detected. Compared with the group with maxillary expansion alone, osteogenic activity was relatively enhanced, whereas osteoclast activity was relatively weakened in the groups administered LF, and the phosphorylated-ERK1/2: ERK1/2 and OPG: RANKL expression ratios increased significantly. The difference was more significant in the group administered LF intramaxillary. Administration of LF promoted osteogenic activity at MPS and inhibited osteoclast activity during maxillary expansion and relapse in rats, which may have occurred through regulation of the ERK1/2 pathway and the OPG-RANKL-RANK axis. The efficiency of intramaxillary LF injection was greater than that of intragastric LF administration.

Myopia Is Suppressed by Digested Lactoferrin or Holo-Lactoferrin Administration.

Myopia is becoming a leading cause of vision impairment. An effective intervention is needed. Lactoferrin (LF) is a protein that has been reported to inhibit myopia progression when taken orally. This study looked at the effects of different forms of LF, such as native LF and digested LF, on myopia in mice. Mice were given different forms of LF from 3 weeks of age, and myopia was induced with minus lenses from 4 weeks of age. Results showed that mice given digested LF or holo-LF had a less elongated axial length and thinned choroid, compared to those given native-LF. Gene expression analysis also showed that the groups given native-LF and its derivatives had lower levels of certain cytokines and growth factors associated with myopia. These results suggest that myopia can be more effectively suppressed by digested LF or holo-LF than native-LF.

ХАРАКТЕРИСТИКА ПОВРЕЖДЕНИЯ МОЗГА ПОСЛЕ γ, n-ОБЛУЧЕНИЯ ГОЛОВЫ МЫШЕЙ И МОДИФИКАЦИЯ УРОВНЯ НЕЙРОВОСПАЛЕНИЯ ПРИ ВВЕДЕНИИ ЛАКТОФЕРРИНА

Purpose: To investigate the effect of γ, n-irradiation of the mice head on the brain cells damage, behavior and cognition, and to examine the possibility of using lactoferrin (LF) to alleviate radiation-induced impairments. Material and methods: Mice heads were irradiated in a beam of neutrons and gamma rays from the IR-8 nuclear reactor. The brain cells of control and irradiated mice were isolated using Percoll. Neurons and resting and activated microglia cells were analyzed using the fluorescently labeled antibodies and flow cytometry. The level of DNA double-strand breaks in neurons was determined by γH2AX histone content. Cytokine gene expression in the hippocampus was studied by RT-PCR. Behavior and cognitive functions were studied using the open field, Morris water maze and novel object recognition tests. LF was isolated from female colostrum by preparative ion-exchange chromatography and purified by affinity chromatography on heparin-sepharose. Results: γ, n-Irradiation of the mice head at a dose of 1.5 Gy led to an increase in the level of DNA double-strand breaks in neurons. Twenty-four hours after irradiation the total number of cells and the number of neurons in the isolated fraction of brain cells decreased, but the number of microglial cells remained unchanged. The number of resting and activated microglia did not change within 3–72 h after γ, n-irradiation. The expression level of the TNFα, IL-1β, and IL-6 genes increased 2 months after γ, n-irradiation of the mice head at a dose of 1.5 Gy, indicating the development of neuroinflammation. At this time, irradiated mice demonstrated the anxiety-like behavior and impaired spatial and recognition memory. A single i.p. administration of human LF to mice immediately after γ, n-irradiation of the head did not affect the observed radiation-induced disturbances, but decreased the gene expression levels of TNFα, IL-1β and IL-6 pro-inflammatory cytokines and increased the gene expression level of TGFβ anti-inflammatory cytokine in the hippocampus 2 months after radiation exposure. The obtained results indicate a partial decrease in the level of hippocampal neuroinflammation of irradiated animals treated with LF. Conclusion: γ, n-Irradiation of the mice head at a dose of 1.5 Gy leads to DNA damage of neurons and the decrease in the number of neurons. Microglia cells are more resistant to such radiation exposure. Late after head-only γ, n-irradiation, mice develop neuroinflammation, which is detected by an increase in the pro-inflammatory cytokine gene expression in the hippocampus and also by anxiety-like behavior and impaired cognitive functions. A single LF administration leads to a partial decrease in the neuroinflammation level, but does not affect the other studied parameters. The optimal dosing regimen of LF remains to be determined to preserve cognitive functions after γ, n-irradiation of the brain.

The influence of exogenic lactoferrin on DNA methylation in postimplantation mouse embryos developed from zygotes exposed to bisphenol A

BACKGROUND: Bisphenol A is a chemical agent ubiquitous in plastic consumer products and a toxin capable of disrupting key epigenetic mechanisms in early embryogenesis. It becomes more and more clear that early development changes in epigenetic pathways caused by exposure to toxic substances are associated with various adult diseases. Therefore the need to identify new agents capable of eliminating epigenetic mechanisms failures caused by the bisphenol A toxin becomes evident. Here we suggest lactoferrin as a normalizer of toxicant-induced epigenomic changes. Currently there is no data on the role of lactoferrin as a normalizer of epigenomic disorders under the influence of toxicants. We assume that in mammalian embryogenesis lactoferrin might function as an epigenetic modulating factor.&#x0D; AIM: The aim of the research is to study effects of lactoferrin on the epigenetic status of postimplantation mouse embryos, exposed to bisphenol A in utero.&#x0D; MATERIALS AND METHODS: In this study, 3 experimental groups of mice and two control group were used. 1. Mice on the first day of pregnancy, injected with 40 mg/kg of body weight of bisphenol A; 2. Mice on the first day of pregnancy, injected with 50 mg/kg of body weight of lactoferrin; 3. Mice on the first day of pregnancy, successively injected with 50 mg/kg body weight of lactoferrin and 40 mg/kg of body weight of bisphenol A. On the 15th day of embryonic development, the level of genome-wide DNA methylation was evaluated in different body parts of the embryos by methyl-sensitive restriction and ImageJ visualization analysis.&#x0D; RESULTS: We demonstrated that in post-implantation mouse embryos, exposure to bisphenol A in the prenatal period caused an increased level of genome-wide DNA methylation. The most prominent effects were observed in brain and abdominal section of the embryos. Together, the present findings confirmed that lactoferrin administration at a dose of 50 mg/kg of body weight resulted in normalization of genome-wide DNA methylation levels after bisphenol A-induced epigenetic alterations.&#x0D; CONCLUSIONS: We assume that lactoferrin may partially neutralize the harmful effects of bisphenol A caused aberrant methylation, and thus can potentially be used as a pharmaceutical product. Factual findings of the present study may help by development of new therapeutic approaches. Nevertheless, further research of the bisphenol A, lactoferrin and lactoferrin + bisphenol A effects on reactive oxygen species and/or antioxidant enzymes is needed.

Protective effect of lactoferrin administration against brain tissue damage in diabetic rats

Bovine lactoferrin (bLf), a glycoprotein with iron, Several of Lf's functions intervene through various cell receptors. Its antibacterial, antiparasitic, anti-inflammatory, and antioxidant effects Additionally, it has been found that Lf has immunomodulating. We looked into the protective effects of Lf on various brain tissue indicators and histopathological examination of streptozotocin (STZ) induced diabetic rats. This research aimed to check the potential protective effect of lactoferrin verses brain lesion in STZ induced diabetic rat. The rats were split into five groups: Control (C), Diabetic rat (T2D), T2D + Insulin, T2D + Lactoferrin, and T2D + Insulin + Lactoferrin. Diabetes was created in rat groups by administration STZ (60 mg/kg body weight), then rat was sacrificed. The tissues of the Brain and serum had been chosen to analyze biochemical brain tissue indicators, Serum Neuron-Specific Enolase (SNE), Serum Brain-Derived Neurotrophic Factor (BDNF), and Tissue Necrosis Factor-Alpha (TNF-Alpha). Also, H&E staining was utilized to measure the histological changes of the brain and Comet assay of brain tissue samples for detection of DNA damage. In T2D rat, Lactoferrin corrected aberrant serum levels of SNE, BDNF and TNF-Alpha, in addition, Lactoferrin improves brain pathological changes might be through hypoglycemic, and/or anti-inflammatory actions and reduced DNA damage as compared to diabetic untreated rats. It could be concluded that oral administration of lactoferrin to diabetic rats alone or in combination with insulin treatment for six weeks was found to attenuate the harmful effects of diabetes on brain biomarkers as well as the pathological lesions that occur in the brain tissues of diabetic rats.

Lactoferrin Restores the Deoxynivalenol-Impaired Spermatogenesis and Blood-Testis Barrier Integrity via Improving the Antioxidant Capacity and Modifying the Cell Adhesion and Inflammatory Response.

Deoxynivalenol (DON) is among the most prevalent contaminants in cereal crops and has been demonstrated to impair male spermatogenesis and induce oxidative stress, testicular apoptosis, and disruption of the blood-testis barrier (BTB). Lactoferrin (LF) is an iron-binding glycoprotein with multifunctions including anti-inflammation and antioxidation. Thus, this study aimed to investigate the effects of LF on the spermatogenesis and integrity of the BTB in DON-exposed mice. Thirty-two male mice were allotted to four groups for a 35-day feeding period: vehicle (basal diet), DON (12 mg/kg), LF (10 mg/d, p.o.), and DON + LF. The results showed that DON induced vacuolization of the spermatogenic epithelium, broke the adhesion junction between Sertoli cells and spermatids established by N-cadherin and induced testicular oxidative stress. LF administration restored sperm production, attenuated the DON-induced oxidative stress and reduced the breakages in adhesion junction. DON exposure enhanced the protein expression of occludin. Transcriptional profiling of the testis observed a disturbance in the expression profiles of cell adhesion and inflammatory response genes, and LF administration reversed these gene expressions. Furthermore, down-regulated signaling pathways, including the apical junction, TNFα signaling via NF-κB, and TGF-β in the DON group were observed. These were restored by LF. Enrichment analysis between DON + LF group and vehicle also confirmed the absence of these pathways. These findings indicated that LF eliminated the DON-induced detriment to spermatogenesis and cell connections between Sertoli cells and spermatids via improving antioxidant capacity and modifying the inflammatory response and cell adhesion genes.

Vitamin D and lactoferrin attenuate stress-induced colitis in Wistar rats via enhancing AMPK expression with inhibiting mTOR-STAT3 signaling and modulating autophagy.

Irritable bowel syndrome (IBS) is a global gastrointestinal disorder closely related to psychological stress exposure and local colonic inflammation. Herein, we investigated the effect of wrap-restraint stress (WRS) on rat behavior, on adenosine monophosphate-activated protein kinase-mammalian/mechanistic target of rapamycin-signal transducer and activator of transcription 3(AMPK-mTOR-STAT3) signaling, and autophagy in colonic mucosa. The impact of chronic administration of vitamin D3 and lactoferrin was compared.Twenty-four male Wistar rats were randomly divided into four groups. Chronic WRS protocol was applied as a rodent model of IBS. Group I: naïve animals, Group II: WRS animals, Group III: WRS-exposed and treated with vitamin D3 (500 IU/kg/day),and Group IV: WRS-exposed and treated with lactoferrin (300 mg/kg/day). In this study, we found that chronic administration of each of vitamin D3 and lactoferrin resulted in a significant increase in social interaction test, interleukin-10, AMPK, optical density of LC3B, goblet cell count and marked decrease in serum cortisol level, STAT3, inflammatory cell count, and optical density of mTOR in comparison to the WRS rats. Our findings suggest that both vitamin D3 and Lactoferrin could augment colonic autophagy through enhanced AMPK expression and inhibition of mTOR-STAT3 signaling, which offers practical insights into their clinical use in the prevention and therapy of IBS. However, lactoferrin intake as a nutritional supplement could be more helpful for stress-induced colitis treatment than vitamin D3.

Human lactoferrin modulates gene expression of the cytokine IL4 and the receptor TLR4 in the rat spleen under stress and upon the lipopolysaccharide administration

ABSTRACT Lactoferrin is a multifunctional glycoprotein of the transferrin family with a molecular mass of about 80 kDa. We studied the effect of human lactoferrin on stress- and lipopolysaccharide-induced changes in blood corticosterone levels, as well as on the gene expression of the cytokine IL4 and the pattern-recognition receptor TLR4 in rat splenocytes. Stress in rats was modeled by swimming in cold water (1-4°C) for 2 min. Lactoferrin and lipopolysaccharide (LPS) were administered intraperitoneally before the stress exposure. Corticosterone level in the plasma was determined by enzyme immunoassay, and changes in gene expression were assessed by real-time polymerase chain reaction (PCR) with reverse transcription. We showed that preventive intraperitoneal administration of lactoferrin reduced the stress and LPS-induced increase in the gene expression of both IL4 and TLR4 in rat splenocytes but did not change the concentration of corticosterone in the blood.

Review, role of lactoferrin in preventing preterm delivery

Prevention of preterm birth (PTB) is a global challenge and is one of the most important issues to be addressed in perinatal care. The hypothesis that ascending lower genital infection leads to PTB has been tested in numerous in vitro and in vivo studies. For patients with intractable vaginitis or high-risk patients with successive PTBs, mainly due to intra-uterine infection, the vaginal flora is enhanced to increase systemic immunity and locally propagate Lactobacillus species. It has been shown that the administration of lactoferrin (LF), a prebiotic with minimum side effects, may be effective in suppressing PTB. This hypothesis has been evaluated in this review using various relevant test examples. The findings suggest that LF may play a role in inflammatory protection in pregnant human cervical tissue. The antibacterial and anti-cytokine effects of LF in human-derived mucus-producing cervical cell lines were also demonstrated. It was also clarified that LF suppresses PTB and improves the prognosis of pups in inflammation-induced PTB animal models. Thus, we have identified that LF, a prebiotic contained in breast milk, can be clinically applied to suppress PTB in humans and to prevent PTBs in high-risk pregnancies.

Effects of human lactoferrin under conditions of neurotoxic exposure: experimental research

BACKGROUND: Translational research using laboratory animals aimed at revealing the features of the pathogenesis of Parkinsons disease serve as a tool for finding new therapeutic strategies.&#x0D; AIM: Was to investigate the effects of human lactoferrin (a multifunctional globular glycoprotein) on behavior the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice as the model of dopaminergic neurons loss.&#x0D; MATERIALS AND METHODS: Nigrostriatal dopaminergic injury was induced by single administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (40 mg/kg) to five-month-old C57Bl/6 mice. Behavioral functions were assessed in the open field and rotarod tests and by the stride length analysis.&#x0D; RESULTS: Preliminary administration of lactoferrin resulted in a significant reduction in the severity of nervous system lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The positive effect of lactoferrin on the exploratory behavior of animals disturbed by neurotoxin, depending on the time of administration, was revealed. Exogenous protein with double preliminary administration had a protective effect on the change in body weight of mice after acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. This suggests a reduction in systemic toxic effects against the background of lactoferrin therapy.&#x0D; CONCLUSION: The results obtained indicate the possibility of the potential use of lactoferrin as a promising therapeutic agent in the treatment of neurodegenerative diseases.