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Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
Bacterial protease alleviate chronic liver fibrosis induced by thioacetamide through suppression of hepatic stellate
Gad Elsayed Mohamed Salem1, Shaimaa M Azzam2, Mona A F Nasser3
1Reef Biology Research Group, Department of Marine Science, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
Abstract:
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.
Insights
Bacterial Protease (BP) shows protective potential against liver fibrosis by reducing inflammation and oxidative stress. This study suggests BP could be a valuable adjuvant therapy for treating liver fibrosis.
Area of Science:
- Biochemistry
- Pharmacology
- Hepatology
Background:
- Chronic liver diseases lead to liver fibrosis due to excessive extracellular matrix accumulation, causing millions of deaths annually.
- Cirrhosis is a significant cause of mortality, necessitating novel therapeutic compounds for chronic liver disease management.
- This study investigates the therapeutic potential of Bacterial Protease (BP) and a novel triazole compound (DPET) against liver fibrosis.
Purpose of the Study:
- To evaluate the anti-inflammatory and antioxidant effects of Bacterial Protease (BP) and DPET in an early-stage liver fibrosis model.
- To assess the impact of BP and DPET on liver function markers, oxidative stress, and inflammatory pathways.
- To determine the efficacy of BP in mitigating thioacetamide-induced liver fibrosis and histopathological damage.
Main Methods:
- Liver fibrosis was induced in male rats using thioacetamide (TAA).
- Animals were divided into six groups: control, BP, TAA, TAA-Silymarin, TAA-BP, and TAA-DPET.
- Key biomarkers including liver enzymes (ALT, AST, ALP), inflammatory cytokines (IL-6, VEGF), oxidative stress markers (MDA, SOD, NO, GSH), and gene expression (MAPK, MCP-1, Nrf2) were analyzed.
Main Results:
- TAA-induced liver fibrosis significantly elevated liver enzymes, IL-6, VEGF, MDA, SOD, and NO, while decreasing GSH.
- TAA treatment led to MAPK and MCP-1 upregulation, Nrf2 downregulation, and significant histopathological damage, including collagen deposition.
- Bacterial Protease (BP) treatment ameliorated TAA-induced liver damage, improved histological architecture, and reduced fibrosis markers.
Conclusions:
- Bacterial Protease (BP) demonstrates significant protective effects against liver fibrosis.
- BP effectively attenuates inflammation and oxidative stress associated with liver fibrosis.
- BP shows potential as an adjuvant therapy for managing hepatic fibrosis.
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