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

Document Type : Original Article

Authors

Department of Biology, Faculty of Science, Eskişehir Technical University, Eskişehir, Turkey

Abstract

Objective: The present study aims to investigate the role of breast cancer-susceptibility gene 1 (BRCA1) protein in the
β-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 4
equal 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 western
blot analysis and confirmed by quantitative immunofluorescence. Proliferating cell nuclear antigen (PCNA), nuclear
factor erythroid 2–related factor (Nrf2) and 8-OHdG protein levels were also determined by the immunofluorescence
analysis. The alkaline comet assay was performed. superoxide dismutase (SOD), catalase (CAT) and membrane lipid
peroxidation 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+LPS
group, expression of BRCA1 protein was over 2 folds higher than the control. After the LPS induction, the DNA strand
breaks, oxidative DNA lesions and abnormal proliferation of the liver cells were almost entirely suppressed in βG preadministrated
animals, indicating the BRCA1 mediated ubiquitination of PCNA and activation of the DNA damage repair
pathways. Activation of Nrf2 in the βG+LPS group resulted in an increase in the levels of Nrf2 pathway dependent
antioxidant enzymes SOD and CAT, prevented the peroxidation of membrane lipids and maintained the histological
architecture of the liver.
Conclusion: The results manifested that the βG is a strong inducer of the BRCA1 protein expression in the LPSinduced
hepatic stress and the protein constitutes the key component of a βG mediated liver protection against an
LPS-induced genotoxic and pathological damage.

Keywords

Main Subjects

References

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Cell Journal (Yakhteh)
Volume 25, Issue 9 - Serial Number 116
September 2023
Pages 645-654

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