期刊
TOXICOLOGICAL SCIENCES
卷 81, 期 1, 页码 43-49出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfh195
关键词
kojic acid; hepatocarcinogenesis; hepatic tumor; promotion
类别
Kojic acid (KA) has been used as a food additive for preventing enzymatic browning of crustaceans and as a cosmetic agent for skin whitening. In the present experiments, effects of KA on the induction of hepatic pre-neoplastic lesions in N-bis(2-hydroxypropyl)nitrosamine-initiated (experiment 1) and non-initiated (experiment 2) models, and its promoting influence in a medium-term liver bioassay (experiment 3) were investigated at dietary doses of up to 2% in male F344 rats. In experiment 1, 2% KA feeding induced significant increases in numbers (22.3+/-13.0 vs 8.5+/-3.4 in the 0%) and areas (0.37+/-0.29 vs 0.05+/-0.03 in the 0%) of glutathione-S-transferase P form (GST-P)-positive foci and toxic changes such as vacuolation of hepatocytes and microgranulomas. The development of GST-P-positive foci was pronounced in the animals with hepatocellular toxic changes. In experiment 2, numbers (0.65+/-0.57 vs 0.17+/-0.28 in the 0%) and areas (0.005+/-0.005 vs 0.0007+/-0.0012 in the 0%) of GST-P-positive foci and hepatocellular proliferating cell nuclear antigen (PCNA) expression (3.8+/-2.3 vs 2.6+/-0.7 in the 0%) were significantly increased by the 2% treatment. The PCNA-positive hepatocytes were abundantly localized around the vacuolated and granulomatous legions in both experiments 1 and 2. In experiment 3, significant increases in numbers (16.9+/-3.2 vs 8.4+/-2.7 in the 0%) and areas (1.62+/-0.39 vs 0.77+/-0.34 in the 0%) of GST-P-positive foci were again observed with 2% KA. These results demonstrate tumor-promoting and possible hepatocarcinogenic activity of KA at 2%, but the carcinogenic potential is likely to be weak. This study also indicated that enhanced replication of hepatocytes related to toxic changes might be involved as an underlying mechanism.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据