Enhancement of hepatocellular proliferative activity of kojic acid in mice by a simultaneous administration of ascorbic acid.
To examine the tumor modification activity of kojic acid (KA) by sodium ascorbic acid (AA), 5-week-old male ICR mice were administered intraperitoneally with N-diethylnitrosamine (DEN) as an initiation treatment. Two weeks after the initiation treatment, animals were fed basal diet containing 0 (Group 1: DEN alone) or 3% KA (Group 3: DEN+KA), drinking water containing 5,000 ppm AA (Group 2: DEN+AA) or 3% KA and 5,000 ppm AA (Group 4: DEN+KA+AA) for 6 weeks. One week after the administration of KA and/or AA, all mice were subjected to two-thirds partial hepatectomy. At the end of the experimental period, all surviving mice were sacrificed and removed the liver. The liver weights of the Groups 3 and 4 were significantly increased, and the number of proliferating cell nuclear antigen positive hepatocytes and the gene expressions of Ccnc, Ccnd1, Ercc and Cyp7a1 were significantly increased in the Group 4, as compared to the Group 1. These results of the present study suggest that AA enhances the hepatocellular proliferative activity of KA in mice.
Kono
Taichi
T
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 1-38-27-101 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan. gonaku@hotmail.com
Moto
Mitsuyoshi
M
Muguruma
Masako
M
Takahashi
Miwa
M
Jin
Meilan
M
Kenmochi
Yusuke
Y
Yokouchi
Yusuke
Y
Mitsumori
Kunitoshi
K
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004052:Diethylnitrosamine / Q000378:metabolism; D004347:Drug Interactions; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000187:drug effects; D011753:Pyrones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
D000975:Antioxidants; D011753:Pyrones; D012333:RNA, Messenger; D004052:Diethylnitrosamine; C011890:kojic acid; D001205:Ascorbic Acid