Vaginal Lactoferrin Administration Decreases Oxidative Stress in the Amniotic Fluid of Pregnant Women: An Open-Label Randomized Pilot Study

Abstract

Background: Oxidative stress (OxS) has been linked to several pregnancy-related complications. Previous studies demonstrated that lactoferrin (LF) has the ability to modulate inflammation, OxS and the immune function. Therefore, we aimed to observe whether vaginal LF administration was able to decrease OxS in the amniotic fluid (AF) of pregnant women undergoing mid-trimester genetic amniocentesis. Methods: In this open-label clinical study, 60 pregnant women were divided into three groups: CONTROLS (n = 20), not treated with LF; LACTO 4HRS (n = 20), treated with LF 4 h prior to amniocentesis; LACTO 12HRS (n = 20), treated with LF 12 h prior to amniocentesis. Thiobarbituric acid reactive substances (TBARS), total antioxidant status (TAS) and oxidative stress index (OSI) were measured in AF samples. In addition, the in vitro antioxidant activity of LF on a cell line was tested. Results: LF decreased the concentration of TBARS in the AF, with LACTO 4HRS demonstrating the lowest value compared with CONTROLS (P < 0.0001). LACTO 4HRS had higher TAS and lower OSI than CONTROLS (P < 0.0001 for both). In vitro, LF was effective against the oxidative challenge regardless of the time of pretreatment. Conclusion: In conclusion, LF decreased both in vivo and in vitro OxS. LF administration may represent an intriguing clinical solution as an adjuvant to treat complications of pregnancy related to inflammation and OxS.

A Review on Lactoferrin and Central Nervous System Diseases

“…Increasing numbers of studies indirectly suggest that the Lf-mediated neuroprotection against neurodegenerative disorders is attributed to its biological characteristics. (1) In inflamed tissues, the content of Lf is significantly increased [60], and Lf can reduce the expression of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 to exert its anti-inflammatory effects [61]; (2) Lf can significantly increase the content of superoxide dismutase (SOD) and reduce the generation of ROS by inhibiting the Fenton reaction [16], thereby exerting ROS modulator effects; (3) Lf can regulate the expression of proteins involved in lipid degradation by controlling the activity of the cAMP/extracellular regulatory protein kinase (ERK) signaling pathway via LRP1 [28], thereby regulating lipid metabolism; (4) increased LfR expression in the brains of patients with neurodegenerative diseases suggests that Lf may play a significant role in the pathogenesis and prevention of neurodegenerative diseases [62]; (5) Lf acts as a normoxic mimetic of hypoxia that is capable of stabilizing hypoxia-inducible factor 1α (HIF-1α) [63] (6); Lf elevates the mRNA and protein levels of brain-derived neurotrophic factor (BDNF) and components of its signaling pathway [64].…”

“…Lf is a multifunctional protein. In addition to its well-known function of regulating iron homeostasis [ 14 ], Lf also exerts multiple important biological effects, such as anti-inflammatory, antibacterial, reactive oxygen species (ROS) modulator, antiviral, and antitumor immunity effects [ 1 , 2 , 4 , 5 , 12 , 15 , 16 ]. These activities are largely mediated by the capacity of Lf to bind iron [ 7 , 17 , 18 , 19 ] and the binding constant [ 20 , 21 , 22 ].…”

The Immunological Role of the Placenta in SARS-CoV-2 Infection—Viral Transmission, Immune Regulation, and Lactoferrin Activity

“…In women taking BLF, pregnancy lasted longer [ 196 ]. Moreover, LF normalized the composition of the vaginal microbiota, cervical tension, extinguished local inflammation, regulated the level of pro-and anti-inflammatory factors (including cytokines, metalloproteinases, and prostaglandins), and protected against oxidative stress, which translated into the overall improvement of the clinical condition of patients and prolonged pregnancy that resulted in delivery on time [ 197 , 198 , 199 ]. Maternal LF, as a regulator of redox homeostasis, may play a pivotal role in the clinical management of COVID-19 during pregnancy.…”

“…LF forms a barrier between mother and fetus as a multi-functional regulator of the immune response with a broad spectrum of activity [ 197 , 198 , 199 ]. Regulation of the effects of LF on inflammatory mediators plays a key role in developing clinical therapies for the consequent cytokine storm and severe infection effects on pregnancy during COVID-19.…”

Lactoferrin for Prevention and Treatment of Anemia and Inflammation in Pregnant Women: A Comprehensive Review

“…In turn, in rabbit preterm delivery models induced by bacteria, intravaginal LTF administration increased fetal survival and extended pregnancy by inhibition of matrix metalloproteinase activity [ 97 ]. In nine clinical trials 217 patients were investigated with diagnosed vaginal infection/inflammation, or liable to infection following invasive diagnostic procedures (amniocentesis) [ 80 , 81 , 95 , 98 , 99 , 100 , 101 , 102 , 103 ]. The administration of LTF normalized composition of vaginal microbiota, tonus of uterus cervix, silenced local inflammatory state, regulated the level of pro- and anti-inflammatory mediators, including cytokines, metalloproteinases and prostaglandins, and protected against oxidative stress.…”