Cell Journal (Sep 2023)

β-Glucan Regulates Lipopolysaccharide Induced Genotoxic Damage to The Liver through The Induction of BRCA1 Protein Expression

  • Gözde Aydoğan Kılıç,
  • Mojahed Alsafi

DOI
https://doi.org/10.22074/cellj.2023.1989382.1226
Journal volume & issue
Vol. 25, no. 9
pp. 645 – 654

Abstract

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Objective: The present study aims to investigate the role of breast cancer-susceptibility gene 1 (BRCA1) protein in theβ-Glucan (βG) molecule mediated regulation of lipopolysaccharide (LPS)-induced liver genotoxicity.Materials and Methods: In this experimental study, totally, 32 male Swiss Albino mice were randomly divided into 4equal groups: control (C), LPS-administered (LPS), βG-administered (βG) and βG-pre-administered/LPS-administered(βG+LPS). The βG was injected at the dose of 150 mg/kg/day intraperitoneally (i.p.) for 3 days. A single dose of 4 mg/kg (i.p.) LPS was administered 24 hours after the last βG injection. BRCA1 expression was determined by westernblot analysis and confirmed by quantitative immunofluorescence. Proliferating cell nuclear antigen (PCNA), nuclearfactor erythroid 2–related factor (Nrf2) and 8-OHdG protein levels were also determined by the immunofluorescenceanalysis. The alkaline comet assay was performed. superoxide dismutase (SOD), catalase (CAT) and membrane lipidperoxidation were biochemically measured, and light microscopic histology was evaluated.Results: The BRCA1 expression level was significantly decreased in the LPS group. However, in the βG+LPSgroup, expression of BRCA1 protein was over 2 folds higher than the control. After the LPS induction, the DNA strandbreaks, oxidative DNA lesions and abnormal proliferation of the liver cells were almost entirely suppressed in βG preadministratedanimals, indicating the BRCA1 mediated ubiquitination of PCNA and activation of the DNA damage repairpathways. Activation of Nrf2 in the βG+LPS group resulted in an increase in the levels of Nrf2 pathway dependentantioxidant enzymes SOD and CAT, prevented the peroxidation of membrane lipids and maintained the histologicalarchitecture of the liver.Conclusion: The results manifested that the βG is a strong inducer of the BRCA1 protein expression in the LPSinducedhepatic stress and the protein constitutes the key component of a βG mediated liver protection against anLPS-induced genotoxic and pathological damage.

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