期刊
HUMAN & EXPERIMENTAL TOXICOLOGY
卷 29, 期 4, 页码 303-309出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/0960327110361757
关键词
hepatotoxic pyrrolizidine alkaloid; clivorine; rat hepatocytes; oxidative stress; antioxidant enzymes
类别
资金
- National Natural Science Foundation of China [30530840 and 30801544]
- Innovation Program of Shanghai Municipal Education Commission [09ZZ125]
- Science and Technology Commission of Shanghai Municipality [07QA14049]
Clivorine is an otonecine-type hepatotoxic pyrrolizidine alkaloid (HPAs), to which humans are exposed when consuming herbs containing such components. In the present study, we investigated clivorine-induced oxidative stress injury on primary cultured rat hepatocytes. Rat hepatocytes were treated with various concentrations of clivorine (1-100 mu M) for 48 hours, and then cell viability was detected by 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay, while lipid peroxidation (LPO) level, glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) activities were determined to evaluate the oxidative injury. The results of MTT assay showed that clivorine decreased cell viability in a concentration-dependent manner. Clivorine also increased LPO amounts in rat hepatocytes at the concentrations of 50 mu M and 100 mu M. Further results showed that clivorine decreased GPx, GST and GR activities, which are all reduced glutathione (GSH)-related antioxidant enzymes. CAT and SOD are both important antioxidant enzymes, and the results showed that clivorine increased CAT activity at the low concentration of 5 mu M and decreased cellular SOD activity at all concentrations. Taken together, our results demonstrated that clivorine induced toxicity on primary cultured rat hepatocytes by causing the damage on cellular redox balance.
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