Antioxidant enzymatically modified isoquercitrin suppresses the development of liver preneoplastic lesions in rats induced by beta-naphthoflavone.
To investigate the modifying effect of enzymatically modified isoquercitrin (EMIQ) on hepatocellular tumor promotion induced by beta-naphthoflavone (BNF) treatment, male rats were administered a single intraperitoneal injection of N-diethylnitrosamine (DEN) and were fed a diet containing BNF (0.5%) for 6 weeks with or without EMIQ (0.2%) in the drinking water after DEN initiation. One week after the commencement of the administration of BNF, rats were subjected to a two-thirds partial hepatectomy. The number and area of GST-P positive foci, the number of COX2-positive cells and the area of elastica-van Gieson (EVG)-positive connective tissue fibers promoted by BNF were significantly suppressed by the administration of the antioxidant EMIQ. Real-time RT-PCR analysis revealed that EMIQ treatment decreased mRNA expression levels of Gstm1, Serpine1, Cox2 and Nfkbia and increased mRNA expression levels of Yc2 compared with those in the DEN-BNF group. These results suggest that co-administration of EMIQ suppresses the hepatocellular tumor-promoting activity of BNF in rats through the anti-inflammatory effects of EMIQ and restores the cellular redox balance altered by BNF.
Shimada
Yuko
Y
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwaicho, Fuchu-shi, Tokyo 183-8509, Japan.
Dewa
Yasuaki
Y
Ichimura
Ryohei
R
Suzuki
Terumasa
T
Mizukami
Sayaka
S
Hayashi
Shim-mo
SM
Shibutani
Makoto
M
Mitsumori
Kunitoshi
K
D000818:Animals; D016588:Anticarcinogenic Agents; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D003238:Connective Tissue / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D008297:Male; D011230:Precancerous Conditions / Q000473:pathology / Q000517:prevention & control*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019324:beta-Naphthoflavone / Q000037:antagonists & inhibitors* / Q000633:toxicity*
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D012333:RNA, Messenger; C016527:isoquercitrin; D019324:beta-Naphthoflavone; D011794:Quercetin; D005979:Glutathione Peroxidase; D051546:Cyclooxygenase 2