Mohannad A Almikhlafi, May A Alsayb, Sara A Almadani, Tahani Saeedi, Mohammed H Alsubhi, Alyaa Farouk Hessin, Marwa Mahmoud Fawzy Atta, Reda Ms Korany, Hany M Fayed, Sally A El Awdan, Hossein M Elbadawy
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引用次数: 0
Abstract
Objective: Liver fibrosis is a progressive consequence of chronic injury with limited treatment options. Vildagliptin (Vilda), a dipeptidyl peptidase-4 inhibitor, possesses antioxidant and anti-inflammatory properties, but its effects on thioacetamide (TAA)-induced liver fibrosis are not fully characterized. This study evaluated Vilda in TAA-treated male rats by assessing hepatic function, oxidative stress, and signaling markers.
Methods: Rats received TAA (100 mg/kg, i.p., twice weekly for 6 weeks) alone or with Vilda (10 or 20 mg/kg, p.o., daily during weeks 3-6). Serum biochemistry, hepatic antioxidants, and specific protein concentrations (AMPK, p-AMPK, SIRT1, Nrf2, STAT3, p-STAT3, TGF-β1, and AFP) were measured. Liver sections were assessed via H&E, qualitative Masson's trichrome, and immunohistochemistry for p-AKT and SIRT1.
Results: TAA impaired liver function, altered lipid profiles, increased oxidative stress, and induced histopathological injury with collagen deposition. These changes coincided with altered hepatic AMPK/SIRT1/Nrf2 and STAT3/TGF-β1-associated markers, alongside PGC-1α and KEAP1 mRNA expression. Vilda treatment was associated with dose-dependent improvements in biochemical, oxidative-stress, and histopathological findings, alongside shifts in inflammation- and fibrosis-associated markers. Vilda was also associated with increased SIRT1 and reduced p-AKT immunoreactivity.
Conclusion: Vilda treatment was associated with attenuation of TAA-induced hepatic injury and fibrotic changes in parallel with modulation of AMPK/SIRT1/Nrf2 and STAT3/TGF-β1-related markers. Because quantitative collagen morphometry and pathway-intervention experiments were not performed, these findings represent associations rather than confirmed causal mechanisms. Further studies are required to define the precise molecular interactions and translational potential of Vilda as an antifibrotic agent.
期刊介绍：
The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal.
The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome.
With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more.
Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).
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