کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5559347 1561565 2017 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Hesperidin protects against chemically induced hepatocarcinogenesis via modulation of Nrf2/ARE/HO-1, PPARγ and TGF-β1/Smad3 signaling, and amelioration of oxidative stress and inflammation
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Hesperidin protects against chemically induced hepatocarcinogenesis via modulation of Nrf2/ARE/HO-1, PPARγ and TGF-β1/Smad3 signaling, and amelioration of oxidative stress and inflammation
چکیده انگلیسی
Hesperidin is a plant-derived bioflavonoid with promising antitumor efficacy, though the underlying mechanisms of action remain poorly elucidated. Thus, we evaluated the in vivo chemopreventive effect of hesperidin against diethylnitrosamine (DEN)-induced hepatocarcinogenesis. We demonstrated the modulatory effect of hesperidin on Nrf2/ARE/HO-1, PPARγ and TGF-β1/Smad3 signaling. Hepatocarcinogenesis was initiated with DEN and promoted with carbon tetrachloride (CCl4). DEN/CCl4-induced rats were treated with 50 and 100 mg/kg hesperidin throughout the experiment. The results revealed that hesperidin significantly reduced circulating liver function marker enzymes, bilirubin, tumor markers and tumor necrosis factor alpha. Hesperidin prevented liver morphological damage, proliferating cell nuclear antigen (PCNA) expression and oxidative stress as evidenced by the reduced lipid peroxidation and enhanced antioxidant defenses. Liver NF-κB and TGF-β1 expression, and Smad3 phosphorylation were significantly up-regulated in DEN/CCl4-induced rats. Hesperidin dramatically abolished NF-κB and TGF-β1/Smad3 signaling as well as collagen deposition in the liver of DEN/CCl4-induced rats. In addition, hesperidin markedly up-regulated the expression of Nrf2, HO-1 and PPARγ in the liver of DEN/CCl4-induced rats. In conclusion, hesperidin can inhibit hepatocarcinogenesis by suppressing oxidative stress, inflammation, cell proliferation, TGF-β1/Smad3 signaling and collagen deposition. These effects are suggested to be mediated by activating Nrf2/ARE/HO-1 and PPARγ pathways.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 277, 1 November 2017, Pages 146-158
نویسندگان
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