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

Alessandro Trentini, Martina Maritati, Valentina Rosta, Carlo Cervellati, Maria Cristina Manfrinato, Stefania Hanau, Pantaleo Greco, Gloria Bonaccorsi, Tiziana Bellini, Carlo Contini, Alessandro Trentini, Martina Maritati, Valentina Rosta, Carlo Cervellati, Maria Cristina Manfrinato, Stefania Hanau, Pantaleo Greco, Gloria Bonaccorsi, Tiziana Bellini, Carlo Contini

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. Trial Registration: Clinicaltrials.gov, NCT02695563. Registered 01 March 2016-Retrospectively registered, https://ichgcp.net/clinical-trials-registry/NCT02695563.

Keywords: amniotic fluid; inflammation; lactoferrin; oxidative stress; pregnancy complications.

Copyright © 2020 Trentini, Maritati, Rosta, Cervellati, Manfrinato, Hanau, Greco, Bonaccorsi, Bellini and Contini.

Figures

Figure 1
Figure 1
Protein concentration (A) and MDA equivalents normalized by total protein (TBARS, B), determined in AF of pregnant women undergoing amniocentesis. CONTROLS (n = 20): women not treated with lactoferrin; LACTO 4HRS (n = 20): women treated with lactoferrin 4 h before amniocentesis; LACTO 12HRS (n = 20): women treated with lactoferrin 12 h before amniocentesis.
Figure 2
Figure 2
Total antioxidant status TAS (A), TAS normalized by protein concentration (B), and oxidative stress index (OSI, C) determined in AF of pregnant women undergoing amniocentesis. CONTROLS (n = 20): women not treated with lactoferrin; LACTO 4HRS (n = 20): women treated with lactoferrin 4 h before amniocentesis; LACTO 12HRS (n = 20): women treated with lactoferrin 12 h before amniocentesis.
Figure 3
Figure 3
MDA equivalents measured in cells treated 4 h (open bar) or 12 h (gray bar) with lactoferrin, or not treated as a control (black bar), and subjected to oxidative challenge with hydrogen peroxide. Values are normalized by the control and the data represent the mean ± SD of 3 independent experiments.

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