Inhibitory effect of curcumin on early liver regeneration following partial hepatectomy in rats.
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.
Seehofer
Daniel
D
Department of General, Visceral, and Transplant Surgery, Charité Campus Virchow, Berlin, Germany. daniel.seehofer@charite.de
Schirmeier
Anja
A
Bengmark
Stig
S
Carter
Jessica
J
Koch
Martin
M
Glanemann
Matthias
M
Nüssler
Andreas K
AK
Neuhaus
Peter
P
Menger
Michael D
MD
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
D000975:Antioxidants; D003474:Curcumin