Bacterial protease alleviate chronic liver fibrosis induced by thioacetamide through suppression of hepatic stellate cells consequently decrease its proliferative index

• Published in: International journal of biological macromolecules 2023-06, Vol.239, p.124243-124243, Article 124243
• Main Authors: Salem, Gad Elsayed Mohamed, Azzam, Shaimaa M., Nasser, Mona A.F., El Malah, Tamer, Abd El-Latief, Hanan M., Khan, Rizwan Hasan, Chavanich, Suchana, Anwar, Hend Mohamed
• Format: Article
• Language: English
• Subjects: adjuvants; Animals; Anti-Inflammatory Agents - pharmacology; antioxidants; Bacillus cereus; collagen; death; Endopeptidases - metabolism; extracellular matrix; Fibrosis; Hepatic Stellate Cells; histology; histopathology; interleukin-6; Liver; liver cirrhosis; Liver Cirrhosis - chemically induced; Liver Cirrhosis - drug therapy; Liver Cirrhosis - metabolism; liver function; Male; males; mutants; Nrf2/MCP-1; Oxidative Stress; Peptide Hydrolases - metabolism; Protease; proteinases; Rats; therapeutics; Thioacetamide; Thioacetamide - toxicity; Vascular Endothelial Growth Factor A - metabolism; VEGF
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2023.124243

In chronic liver diseases, liver fibrosis occurs due to excessive extracellular matrix (ECM) protein accumulation. Approximately 2 million deaths occur yearly due to liver disease, while cirrhosis is the 11th most common cause of death. Therefore, newer compounds or biomolecules must be synthesized to treat chronic liver diseases. In this aspect, the present study focuses on the assessment of the anti-inflammatory and antioxidant impact of Bacterial Protease (BP) produced by a new mutant strain of bacteria (Bacillus cereus S6-3/UM90) and 4,4′-(2,5-dimethoxy-1,4-phenylene) bis (1-(3-ethoxy phenyl)-1H-1,2,3-triazole) (DPET) in the treatment of early stage of liver fibrosis induced by thioacetamide (TAA). Sixty male rats were divided into six groups, ten rats each as follows: (1) Control group, (2) BP group, (3) TAA group, (4) TAA-Silymarin (S) group, (5) TAA-BP group, and (6) TAA-DPET group. Liver fibrosis significantly elevated liver function ALT, AST, and ALP, as well as anti-inflammatory interleukin 6 (IL-6) and VEGF. The oxidative stress parameters (MDA, SOD, and NO) were significantly increased with a marked reduction in GSH. Expression of MAPK and MCP-1 was unregulated in the TAA group, with downregulation of Nrf2 was observed. TAA caused histopathological alterations associated with hepatic vacuolation and fibrosis, increasing collagen fibers and high immuno-expression of VEGF. On the other hand, treatment with BP successfully improved the severe effects of TAA on the liver and restored histological architecture. Our study concluded the protective potentials of BP for attenuating liver fibrosis and could be used as adjuvant therapy for treating hepatic fibrosis. [Display omitted]