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Kolaviron inhibits dimethyl nitrosamine-induced liver injury by suppressing COX-2 and iNOS expression via NF-κB and AP-1

Cited 93 time in Web of Science Cited 114 time in Scopus
Authors
Farombi, Ebenezer O.; Shrotriya, Sangeeta; Surh, Young-Joon
Issue Date
2009-01
Citation
Life Sciences, Vol.84 No.5-6, pp.149-155
Keywords
KolavironDimethyl nitrosamineHepatotoxicityCOX-2iNOSNF-kappa BAP-1
Abstract
Aims: Kolaviron, a bioflavonoid isolated from the seeds of Garcinia kola has been reported to possess anti-inflammatory, antioxidant, antigenotoxic and hepatoprotective activities in model systems via multiple biochemical mechanisms. The present study investigated the possible molecular mechanisms underlying the hepato protective effects of kolaviron. Main methods: Biomarkers of hepatic oxidative injury, histological and immunohistochemical techniques were used. In addition, the protein expression levels of cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) were evaluated by western blotting while DNA-binding activities of nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1) were determined by electrophoretic mobility shift assay. Key findings: Kolaviron administered orally at doses of 100 and 200 mg/kg for 7 days significantly lowered the activities of serum transaminases and gamma-glutamyl tranferase induced by single intraperitoneal administration of dimethyl nitrosamine (DMN) (20 mg/kg) and preserved the integrity of the hepatocytes. Also, kolaviron at both doses reduced the DMN induced elevated hepatic levels of malondialdehyde and reversed DMN mediated decrease in hepatic glutathione. The hepatoprotective effect of kolaviron was compared to that of curcumin. an established hepatoprotective agent. Kolaviron inhibited the DMN induced expression of COX-2 and iNOS. Immunohistochemical staining of rat liver verified the inhibitory effect of kolaviron on DMN-induced hepatic COX-2 expression. Furthermore, kolaviron abrogated DMN induced binding activity of NF-kappa B as well as AP-1 Significance: The ability of kolaviron to inhibit COX-2 and iNOS expression through down regulation of NF-kappa B and AP-1 DNA binding activities could be a mechanism for the hepatoprotective properties of kolaviron. (c) 2008 Published by Elsevier Inc.
ISSN
0024-3205
URI
https://hdl.handle.net/10371/172813
DOI
https://doi.org/10.1016/j.lfs.2008.11.012
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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