In vitro heme and non-heme iron capture from hemoglobin, myoglobin and ferritin by bovine lactoferrin and implications for suppression of reactive oxygen species in vivo

Abstract

Lactoferrin (Lf), present in colostrum and milk is a member of the transferrin family of iron-binding glyco-proteins, with stronger binding capacity to ferric iron than hemoglobin, myoglobin or transferrin. Unlike hemoglobin and myoglobin, iron-bound Lf is reasonably stable to gastric and duodenal digestive conditions. Unlike ferrous iron, ferric iron is not directly reactive with oxygen supporting the capacity of Lf capture of heme iron to suppress reactive oxygen species (ROS) production. We therefore hypothesized that bovine Lf could capture and thereby terminate the cycle of ROS production by heme iron. The transfer of heme iron from either intact or digested forms of hemoglobin and myoglobin and from intact ferritin was demonstrated by in vitro methods, monitoring Fe-saturation status of Lf by changes in absorptivity at 465 nm. The results are discussed in the context of new proposed opportunities for orally administered Lf to regulate oxidative damage associated with heme iron. In addition to potentially suppressing oxidative heme-iron-mediated tissue damage in the lumen, Lf is expected to also reverse the overload of ferritin-bound iron, that accompanies chronic inflammation and aging. These new proposed uses of Lf are additional to known host defense functions that include anti-microbial, anti-viral properties, immune and cancer cell growth regulation. The findings and interpretations presented require clinical substantiation and may support important additional protective and therapeutic uses for Lf in the future.

Bioavailability of a Novel Form of Microencapsulated Bovine Lactoferrin and Its Effect on Inflammatory Markers and the Gut Microbiome: A Pilot Study

“…There are no studies completed using Inferrin TM ; however, a number of studies have been conducted investigating the potential effects of bLF. Cell culture studies have shown a potential role for bLF in inhibiting infection with influenza type 1 and 2 [ 14 ], reducing reactive oxygen species production [ 15 ], improving antimicrobial capacity against a range of microbes including Escherichia coli and Staphylococcus aureus [ 16 ], and causing immunosuppression of dendritic cells [ 17 ]. Animal models also show positive effects of bLF on immune function, including increased immunoglobin A and immunoglobin M production in small intestine epithelial cells of mice [ 18 ], improved natural killer cell production and activity in piglets fed bLF-supplemented formula [ 19 ], decreased expression of tumour necrosis factor alpha in healthy mice [ 20 ], and decreased bacteria load, neutrophils, and pro-inflammatory cytokines in mice with acute and chronic lung infections [ 21 ].…”

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

“…Free radical scavenging mechanisms of LF involve stimulated glycolysis, increased ATP generation to sustain ion gradient with membrane potential and morphology of the cell 444 . Oral supplementation of LF could prevent oxidative damage by heme iron and reverse ferritin-bound iron overload during chronic inflammation and aging 445 . Notably, both OxS and related metabolic syndromes are considered as potential risk factors in COVID-19 pathology 446 .…”

Process optimisation of haemoglobin hydrolysis by complex proteases to produce haem‐enriched peptides and its iron uptake property evaluation by Caco‐2 cell model

“…This was in agreement with the result of Zariwala et al (2013), who found that most non-haem iron was insoluble that was difficultly absorbed by small intestine. Jegasothy et al (2014) also suggested that the solubility of digestive complexes of haem iron, but not digestive products of non-haem iron, were important for absorption. In our present study, we also found that the iron solubility of haem-peptides (95.37%) gastric digestates was significantly higher than those of haemoglobin (80.41%), haemin chloride (83.17%) and haemin chloride plus collagen complex (83.70%; P < 0.05), and there was no significant difference between the iron solubility of haemin chloride gastric digested juice and that of haemin chloride plus collagen complex haemin chloride-digested juice (P > 0.05).…”