title: Alteration of AP-endonuclease1 expression in curcumin-treated fibrotic rats.
abstract: BACKGROUND
  Apurinic/apyrimidinic endonuclease1/ redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in DNA base excision repair and redox regulation of many transcription factors. It is an important pro-survival protein activated in response to oxidative stress. Increased level of this essential redox sensitive protein correlates closely with cellular survival against oxidative insults. Curcumin (diferuloylmethane) a naturally occurring compound derived from turmeric has attracted interest because of its anti-inflammatory, anti-oxidative, and chemopreventive activities.
  
  
  METHODS
  The current study evaluates the in vivo role of curcumin in protecting and treating liver injury and fibrogenesis caused by carbon tetrachloride (CCl4) in rats. It also addresses the possible involvement of the multifunctional protein APE1 in hepatoprotection. Analysis of APE1 expression was performed at mRNA and protein levels by reverse transcriptase (RT)-PCR and western blotting respectively. Profile of HSCs-activation related genes were assayed by RT-PCR and pro-inflammatory cytokines levels were determined by enzyme-linked immune assays.
  
  
  RESULTS
  Here we show that oral administration of curcumin was accompanied by a robust increase in APE1 protein and mRNA levels, and improved the histological architecture of rat liver. In addition, curcumin attenuated oxidative stress by increasing the content of hepatic glutathione within normal values, leading to the reduction in the level of lipid hydroperoxide. Curcumin remarkably suppressed inflammation by reducing levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB) and interleukin-6 (IL-6). It also inhibited hepatic stellate cells (HSCs) activation by elevating the level of PPARγ and reducing the abundance of transforming growth factor-β (TGF-β). We found that oral administration of curcumin at 200 mg/kg dose not only protected against CCl4-induced hepatic injury, but also resulted in more than two-fold induction of APE1 protein expression in CCl4-induced rat group.
  
  
  CONCLUSIONS
  It can be concluded that curcumin reduced markers of liver damage in rats treated with CCl4, with concomitant elevation in APE1 protein level indicating a possible protective effect with unknown mechanism. The induction of DNA repair enzymes may be an important and novel strategy for hepatic protection against oxidative injury.
authors.affiliation: Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt. arbassiouny@yahoo.com
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Bassiouny
authors.forename: Amira
authors.initials: A
authors.lastname: Zaky
authors.forename: Kamal M
authors.initials: KM
authors.lastname: Kandeel
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002251:Carbon Tetrachloride; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008054:Lipid Peroxides; D020011:Protective Agents; D012333:RNA, Messenger; D002251:Carbon Tetrachloride; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D005978:Glutathione; D003474:Curcumin