Maltol Mitigates Thioacetamide-induced Liver Fibrosis through TGF-β1-mediated Activation of PI3K/Akt Signaling Pathway
| العنوان: | Maltol Mitigates Thioacetamide-induced Liver Fibrosis through TGF-β1-mediated Activation of PI3K/Akt Signaling Pathway |
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| المؤلفون: | Ying-Ping Wang, Chen Chen, Jin-Gang Hou, Wei Li, Shan Tang, Zhi Liu, Shuang Jiang, Zi Wang, Xiang-xiang Liu, Xiaojie Mi |
| المصدر: | Journal of Agricultural and Food Chemistry. 67:1392-1401 |
| بيانات النشر: | American Chemical Society (ACS), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Liver Cirrhosis, Male, 0106 biological sciences, medicine.medical_treatment, Intraperitoneal injection, Maltol, Thioacetamide, Pharmacology, medicine.disease_cause, 01 natural sciences, Transforming Growth Factor beta1, Superoxide dismutase, Mice, Phosphatidylinositol 3-Kinases, chemistry.chemical_compound, Hepatic Stellate Cells, medicine, Animals, Humans, Aspartate Aminotransferases, PI3K/AKT/mTOR pathway, Mice, Inbred ICR, biology, Superoxide Dismutase, 010401 analytical chemistry, Alanine Transaminase, General Chemistry, Glutathione, 0104 chemical sciences, Oxidative Stress, Liver, chemistry, Pyrones, biology.protein, General Agricultural and Biological Sciences, Hepatic fibrosis, Proto-Oncogene Proteins c-akt, Oxidative stress, Signal Transduction, 010606 plant biology & botany |
| الوصف: | Our previous study has confirmed that maltol can attenuate alcohol-induced acute hepatic damage and prevent oxidative stress in mice. Therefore, maltol might have the capacity to improve thioacetamide (TAA)-induced liver fibrosis. The purpose of this work was to explore the antifibrotic efficacy and underlying mechanisms of maltol for TAA-treated mice. Progressive liver fibrosis was established with a dose-escalating protocol in which the mice received TAA intraperitoneal three times a week for a total duration of 9 weeks. The injection doses of TAA were 50 mg/kg for the first week, 100 mg/kg for the second and third weeks, and 150 mg/kg for the rest of the injections. Maltol with doses of 50 and 100 mg/kg was given by gavage after 4 weeks of intraperitoneal injection of TAA, respectively, once daily for 5 weeks. Results indicated that TAA intraperitoneal injection significantly increased serum activities of alanine aminotransferase (ALT) (52.93 ± 13.21 U/L vs 10.22 ± 3.36 U/L) and aspartate aminotransferase (AST) (67.58 ± 25.84 U/L vs 39.34 ± 3.89 U/L); these elevations were significantly diminished by pretreatment with maltol. Additionally, maltol ameliorated TAA-induced oxidative stress with attenuation in MDA (p < 0.05 or p < 0.01) content; evident elevation in the GSH levels, GSH/GSSG ratio (p < 0.05 or p < 0.01), and superoxide dismutase (SOD) (p < 0.01); and restored liver histology accompanied by a decrease of α-smooth muscle actin (α-SMA) expression. Furthermore, maltol significantly suppressed the transforming growth factor-β1 (TGF-β1) expression and the PI3K/Akt pathway. This study suggested that maltol alleviated experimental liver fibrosis by suppressing the activation of HSCs and inducing apoptosis of activated HSCs through TGF-β1-mediated PI3K/Akt signaling pathway. These findings further clearly suggested that maltol is a potent therapeutic candidate for the alleviation of liver fibrosis. |
| تدمد: | 1520-5118 0021-8561 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ae49d365266090ecc5cc598342eacacd https://doi.org/10.1021/acs.jafc.8b05943 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....ae49d365266090ecc5cc598342eacacd |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15205118 00218561 |
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