Abstract:
:Two-stage rat hepatocarcinogenesis model was used to induce early carcinogenesis in which thioacetamide (TAA) promotes diethylnitrosamine (DEN) initiated carcinogenesis. Dimethyl fumarate (DMF) used to treat multiple sclerosis, activates the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway during oxidative stress, and maintains antioxidant levels. Glibenclamide (GLB), a sulphonylurea drug used to treat type II diabetes, possesses anti-inflammatory properties and inhibits NLRP3 inflammasomes. The present study was designed to investigate the concurrent intervention of DMF and GLB on DEN + TAA-induced early hepatic carcinogenesis. DMF and GLB treatment improved DEN + TAA-induced decrease in body weight, increase in liver weight and plasma transaminases, histopathological alterations, DNA damage, and apoptosis. DMF and GLB intervention significantly ameliorated the DEN + TAA-induced alterations in the antioxidant (Nrf2, HO-1, SOD-1, catalase), inflammatory (NF-κB, NLRP3, ASC, caspase-1), fibrogenic (TGF-β1, collagen) and regenerative proliferative stress (GST-p, HGF, c-MET, TGFα, EGF, AFP) markers. The present results indicate that Nrf2/ARE activation and NLRP3 inhibition might be a rational approach to attenuate oxidative stress and chronic inflammation associated progression of hepatocarcinogenesis.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Dwivedi DK,Jena GBdoi
10.1016/j.bbrc.2019.11.100subject
Has Abstractpub_date
2020-02-05 00:00:00pages
381-387issue
2eissn
0006-291Xissn
1090-2104pii
S0006-291X(19)32226-0journal_volume
522pub_type
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journal_title:Biochemical and biophysical research communications
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journal_title:Biochemical and biophysical research communications
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journal_title:Biochemical and biophysical research communications
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journal_title:Biochemical and biophysical research communications
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journal_title:Biochemical and biophysical research communications
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