title: Hesperidin prevents liver fibrosis in rats by decreasing the expression of nuclear factor-κB, transforming growth factor-β and connective tissue growth factor.
abstract: OBJECTIVE
  To evaluate the antioxidant, immunomodulatory, antinecrotic and antifibrotic effects of hesperidin on CCl4-induced cirrhosis.
  
  
  METHODS
  Liver damage was produced by giving CCl4 injections (0.4 g/kg, i.p., 3 times per week for 8 weeks) to rats. Hesperidin (200 mg/kg) was administered using gavage. The expression of nuclear factor-κB (NF-κB), transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF), interleukin (IL)-10 and IL-1β was assessed using Western blotting. Alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (γ-GTP) serum activities, glycogen content, reduced/oxidised glutathione (GSH/GSSG) ratio, lipid peroxidation degree and fibrosis (using hydroxyproline content and a histopathological analysis) were measured.
  
  
  RESULTS
  CCl4 increased the enzymatic activities of ALT and γ-GTP, liver lipid peroxidation, the hydroxyproline content as well as NF-κB, TGF-β, CTGF, IL-1β and IL-10 levels and decreased the glycogen content and GSH/GSSG ratio. Hesperidin significantly decreased the modifications produced by CCl4, except in the case of IL-10, which was further increased by the flavone. The group receiving hesperidin alone showed decreases in lipid peroxidation, NF-κB, TGF-β, CTGF and IL-1β and an increase in IL-10. The results of the histopathological analysis were in agreement with the biochemical and molecular findings.
  
  
  CONCLUSIONS
  This study demonstrates that hesperidin prevents experimental necrosis and fibrosis. The action mechanism of hesperidin is associated with its ability to reduce oxidative stress and modulate proinflammatory and profibrotic signals. These results support earlier findings demonstrating the beneficial effect of hesperidin against liver damage.
authors.affiliation: Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.
authors.forename: J Eliuth
authors.initials: JE
authors.lastname: Pérez-Vargas
authors.forename: Natanael
authors.initials: N
authors.lastname: Zarco
authors.forename: Mineko
authors.initials: M
authors.lastname: Shibayama
authors.forename: José
authors.initials: J
authors.lastname: Segovia
authors.forename: Víctor
authors.initials: V
authors.lastname: Tsutsumi
authors.forename: Pablo
authors.initials: P
authors.lastname: Muriel
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D002251:Carbon Tetrachloride; D055513:Connective Tissue Growth Factor / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D006569:Hesperidin / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000235:genetics; D009336:Necrosis / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D002251:Carbon Tetrachloride; D006569:Hesperidin