Lactobacillus acidophilus ATCC 4356 Exopolysaccharides Suppresses Mediators of Inflammation through the Inhibition of TLR2/STAT-3/P38-MAPK Pathway in DEN-Induced Hepatocarcinogenesis in Rats

Abstract

Probiotics have been suggested as a safe and cost-effective approach to prevent or treat hepatocellular carcinoma (HCC). Some of the exopolysaccharides (EPSs) produced by lactic acid bacteria confer health benefits such as immunomodulatory and antitumor activities. The present study was therefore aimed to investigate the immunomodulatory effect of Lactobacillus acidophilus ATCC 4356 EPSs against diethylnitrosamine (DEN) and gamma radiation (IR) induced HCC either as prevention or treatment in male rats’ model. Biochemical results revealed a significant increase in serum ALT and γ-GT activities as well as MDA, IL-17, TGF-β1, signal transducer and activator of transcription-3 protein (STAT3), mitogen-activated protein kinase p38 (p38MAPK) levels in the liver tissue. The gene expression level of the liver toll-like receptor 2 (TLR-2) gene was also increased. However, prevention and treatment with EPSs ameliorated most of the investigated parameters. The histopathological observations of liver tissues were in agreement with restored biochemical results. In conclusion, Lactobacillus acidophilus ATCC 4356 EPSs are efficacious control against HCC throughout the regulation of TLR2/STAT-3/P38-MAPK Pathway associated with inflammation. Therefore, our novel EPSs ATCC 4356 could be used as a good, safe and effective probiotic to prevent hepatocarcinogenesis in suspected patients.

Acknowledgments

Sincerely the authors acknowledge Dr. Osma Mostafa Mostafa (Lecturer of Histopathology, Faculty of Medicine, Al-Azhar University) for accomplishing the Histopathological examination in the present study.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Funding

The authors did not receive support from any organization for the submitted work.

Conflicts of Interest

The authors declare no conflict of interest

Ethics Approval

Animals handling and anesthesia procedures were based on the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines and approved by Institutional Animal Ethics Committee of The National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt. All animal experiments were carried out in accordance with the National Institutes of Health guide for the care and use of laboratory animals (serial: 18-2019).

Author Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Ola Mohmed Sayed Khedr], [Sawsan mohmed El-Sonbaty], [Fatma Sayed Mohmed Moawed], [Eman I. Kandil^] and Basma E. Abdel-Maksoud]. The first draft of the manuscript was written by [Ola Mohmed Sayed Khedr] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.