Protective Role of Mytilus edulis Hydrolysate in Lipopolysaccharide-Galactosamine Acute Liver Injury

Eleonora Starikova, Jennet Mammedova, Arina Ozhiganova, Aleksandra Lebedeva, Anna Malashicheva, Daria Semenova, Evgeniia Khokhlova, Eleonora Mameli, Andrea Caporali, Jimi Wills, Alexey Sokolov

Research output: Contribution to journalArticlepeer-review

Abstract

Acute liver injury in its terminal phase trigger systemic inflammatory response syndrome with multiple organ failure. An uncontrolled inflammatory reaction is difficult to treat and contributes to high mortality. Therefore, to solve this problem a search for new therapeutic approaches remains urgent. This study aimed to explore the protective effects of M. edulis hydrolysate (N2-01) against Lipopolysaccharide-D-Galactosamine (LPS/D-GalN)-induced murine acute liver injure and the underlying mechanisms. N2-01 analysis, using Liquid Chromatography Mass Spectrometry (LCMS) metabolomic and proteomic platforms, confirmed composition, molecular-weight distribution, and high reproducibility between M. edulis hydrolysate manufactured batches. N2-01 efficiently protected mice against LPS/D‑GalN‑induced acute liver injury. The most prominent result (100% survival rate) was obtained by the constant subcutaneous administration of small doses of the drug. N2-01 decreased Vascular Cell Adhesion Molecule-1 (VCAM-1) expression from 4.648±0.445 to 1.503±0.091 MFI and Interleukin-6 (IL-6) production in activated Human Umbilical Vein Endothelial Cells (HUVECs) from 7.473±0.666 to 2.980±0.130 ng/ml in vitro. The drug increased Nitric Oxide (NO) production by HUVECs from 27.203±2.890 to 69.200±4.716 MFI but significantly decreased inducible Nitric Oxide Synthase (iNOS) expression from 24.030±2.776 to 15.300±1.290 MFI and NO production by murine peritoneal lavage cells from 6.777±0.373 μM to 2.175±0.279 μM. The capability of the preparation to enhance the endothelium barrier function and to reduce vascular permeability was confirmed in Electrical Cell-substrate Impedance Sensor (ECIS) test in vitro and Miles assay in vivo. These results
suggest N2-01 as a promising agent for treating a wide range of conditions associated with uncontrolled inflammation and
endothelial dysfunction.
Original languageEnglish
JournalFrontiers in pharmacology
Volume12
Early online date18 May 2021
DOIs
Publication statusE-pub ahead of print - 18 May 2021

Keywords

  • edulis hydrolysate
  • Acute liver injury
  • Vascular permeability
  • Nitric Oxide
  • VCAM-1
  • IL-6

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