Involvement of TLR4/ CXCL9/ PREX-2 pathway in the development of hepatocellular carcinoma (HCC) and the promising role of early administration of lactobacillus plantarum in Wistar rats

• Published in: Tissue & cell 2019-10, Vol.60, p.38-47
• Main Authors: Elshaer, Asmaa M., El-kharashi, Omnyah A., Hamam, Ghada Galal, Nabih, Enas S., Magdy, Yosra M., Abd El Samad, Abeer A.
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Carcinoma, Hepatocellular - etiology; Carcinoma, Hepatocellular - prevention & control; Chemokine CXCL9 - metabolism; Cirrhosis; Complications; CXCL9; Cytokeratin; Hepatocellular carcinoma; Hepatocytes; Intestinal microflora; Lactobacillus; Lactobacillus Plantarum; Liver; Liver - drug effects; Liver - pathology; Liver cirrhosis; Liver Cirrhosis, Experimental - complications; Liver Cirrhosis, Experimental - drug therapy; Liver Cirrhosis, Experimental - metabolism; Liver Neoplasms - etiology; Liver Neoplasms - prevention & control; Male; Microbiota; Microbiota - drug effects; Nuclei (cytology); Plant protection; Probiotics - therapeutic use; Proliferating cell nuclear antigen; Proteinase-activated receptor 1; Rats; Rats, Wistar; Signal Transduction - drug effects; Thioacetamide; Thioacetamide - toxicity; TLR4; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors
• ISSN: 0040-8166; 1532-3072
• DOI: 10.1016/j.tice.2019.07.010

•Gut microbiota play an important role in maintenance of gut liver axis.•Liver cirrhosis may be complicated by carcinoma through disturbance in gut microbiota.•TLR4/CXCL9/PREX-2 may be implicated in the progression of cirrhosis to carcinoma.•Probiotics may improve cirrhosis and prevent its progression to carcinoma through modulation of TLR4/CXCL9/PREX-2 pathway. Improvement of gut microbiota may help in preventing the progression of cirrhosis. We supposed that Lactobacillus Plantarum (L. Plantarum) protects the cirrhotic liver through suppression of TLR4/ CXCL9/ PREX-2. Rats were divided into two groups. Group I, lasts for six weeks and Group II lasts for 12 weeks. Each group was subdivided into: naïve, Lactobacillus Plantarum (L. Plantarum), thioacetamide (TAA) and TAA + L. Plantarum. Liver function tests, α fetoprotein (AFP) levels, CXCL9, PREX-2 and TLR4 expression were assessed. Histological studies were performed. TAA induced significant deterioration in liver functions and increased AFP. There was periportal cirrhosis, vacuolated hepatocytes, decrease hepatocyte parrafin-1 (hep par-1) expression, increase proliferating cell nuclear antigen (PCNA) positive nuclei and cytokeratin AE1/AE3. The PCR results showed significant increase in TLR4, CXCL9 and PREX-2 expression. Early administration of L. Plantarum significantly decreased the expression of TLR4, CXCL9 and PREX-2 together with improvement in liver function and prevented the pathological changes. The cirrhotic complications induced by TAA are through activation of TLR4/ CXCL9/ PREX-2 pathway and could be prevented by the early administration of L. Plantarum.