title: Inhibitory effect of curcumin on early liver regeneration following partial hepatectomy in rats.
abstract: BACKGROUND
  Curcumin (Cur) is a nontoxic, hepatoprotective antioxidant. Recent investigations have demonstrated a protective effect of curcumin pretreatment during cold ischemia of hepatocytes, but its impact on liver regeneration per se has not been investigated so far.
  
  
  METHODS
  Male Sprague-Dawley rats (n = 6 per group) underwent sham operation, 70% partial hepatectomy (PH), or PH with curcumin application (100 mg per kg bodyweight per day) starting 48 h before surgery. Rats were sacrificed 24 h after surgery. Liver regeneration was analyzed by measurement of relative liver weight, mitotic-index, bromo-deoxy-uridine (BrdU)-incorporation and Ki-67 expression.
  
  
  RESULTS
  The relative liver weight 24 h after surgery was similar in the PH groups with and without curcumin treatment. Also, a comparably high number of Ki-67 positive proliferating hepatocytes was detected in both groups. In contrast, the mitotic index in the untreated PH group (83 +/- 20 mitosis/2000 hepatocytes) was significantly higher than in the curcumin treated group (21 +/- 6). The BrdU labeling index was slightly higher in the curcumin treated group with PH (24% +/- 5%) than in the untreated group (16% +/- 2%). The hepatocyte density as marker of cellular hypertrophy was significantly lower in the curcumin group (474 +/- 23) than in the untreated group (609 +/- 22).
  
  
  CONCLUSIONS
  Curcumin inhibits cell cycle progression during normal liver regeneration in rats, predominantly at the level of the G2/M transition point. However, the total liver mass and function was not significantly altered. Nevertheless, application of curcumin in conditions of high physiological cell proliferation should be performed with caution.
authors.affiliation: Department of General, Visceral, and Transplant Surgery, Charité Campus Virchow, Berlin, Germany. daniel.seehofer@charite.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Seehofer
authors.forename: Anja
authors.initials: A
authors.lastname: Schirmeier
authors.forename: Stig
authors.initials: S
authors.lastname: Bengmark
authors.forename: Jessica
authors.initials: J
authors.lastname: Carter
authors.forename: Martin
authors.initials: M
authors.lastname: Koch
authors.forename: Matthias
authors.initials: M
authors.lastname: Glanemann
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Nüssler
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D003474:Curcumin