title: Diosmin abrogates chemically induced hepatocarcinogenesis via alleviation of oxidative stress, hyperproliferative and inflammatory markers in murine model.
abstract: Hepatocellular carcinoma (HCC) is a global health problem and is fourth leading cause of cancer related deaths. Now-a-days new strategies have been accounted for the chemoprevention of liver cancer due to ineffective traditional treatments against HCC. In the present study, we have shown that diosmin attenuates 2-AAF induced hepatic toxicity and early tumor promotion markers (ODC, PCNA and Ki67), its chemopreventive efficacy against DEN initiated and 2-AAF promoted hyper-proliferation and hepatocarcinogenesis in Wistar rats. Hepatocarcinogenesis has been characterized by the presence of apparent hepatic nodules, hepatic proliferation, elevation in the levels of proliferation markers (PCNA and Ki67), and inflammatory markers (COX-2 and iNOS) in DEN and 2-AAF administered rats. Protective efficacy of diosmin has been investigated in terms of its potential in reducing the percentage of visible hepatic nodules and the restoration of early tumor markers (PCNA, Ki67 and ODC), oxidative stress biomarkers, serum cytotoxicity markers (AST, ALT and LDH), cell necrosis markers (NF-kappa B and TNF-α) and inflammatory markers (COX-2 and iNos). Our study demonstrates that the inhibition of cell proliferation and down regulation of inflammatory markers may be, at least in part, the underlying mechanisms related to the liver tumor inhibition by diosmin. The present study allows us to conclude that diosmin being a dietary supplement, could be used as chemopreventive agent to prevent hepatocarcinogenesis.
authors.affiliation: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Mir
authors.initials: M
authors.lastname: Tahir
authors.forename: Muneeb U
authors.initials: MU
authors.lastname: Rehman
authors.forename: Abdul
authors.initials: A
authors.lastname: Lateef
authors.forename: Abdul Quaiyoom
authors.initials: AQ
authors.lastname: Khan
authors.forename: Rehan
authors.initials: R
authors.lastname: Khan
authors.forename: Wajhul
authors.initials: W
authors.lastname: Qamar
authors.forename: Oday
authors.initials: O
authors.lastname: O'Hamiza
authors.forename: Farrah
authors.initials: F
authors.lastname: Ali
authors.forename: Syed Kazim
authors.initials: SK
authors.lastname: Hasan
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
mesh_terms: D015073:2-Acetylaminofluorene / Q000633:toxicity; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000097:blood / Q000378:metabolism; D004052:Diethylnitrosamine / Q000633:toxicity; D004145:Diosmin / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000097:blood / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000097:blood / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000097:blood / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000097:blood / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D018809:Proliferating Cell Nuclear Antigen / Q000097:blood / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D014409:Tumor Necrosis Factor-alpha; D004052:Diethylnitrosamine; D004145:Diosmin; D015073:2-Acetylaminofluorene; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D009955:Ornithine Decarboxylase