Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5848878 | Environmental Toxicology and Pharmacology | 2015 | 8 Pages |
Abstract
Microcystin-LR, which is an inhibitor of serine/threonine protein phosphatase (PP)1 and PP2A, induces liver injury by its selective uptake system into the hepatocyte. It is also thought that microcystin-LR induces reactive oxygen species (ROS). We tried to establish the chemical prevention of microcystin-LR poisoning. We investigated the effect of grapefruit flavanone glycoside naringin on cytotoxicity of microcystin-LR using human hepatocyte uptake transporter OATP1B3-expressing HEK293-OATP1B3 cells. We found cytotoxicity of microcystin-LR was attenuated by naringin in a dose dependent manner. The inhibition magnitude of total cellular serine/threonine protein phosphatase activity induced by microcystin-LR was suppressed by naringin. In addition, uptake of microcystin-LR into HEK293-OATP1B3 cells was inhibited by naringin. Furthermore, microcystin-LR induced phosphorylation of p53 was inhibited by naringin. Regardless of the difference in the exposure pattern of pre-processing and post-processing of naringin, the toxicity of microcystin-LR was comparable. These results suggested that naringin is promising remedy as well as preventive medicine for liver damage with microcystin-LR. In addition, involvement of ROS production after exposure to the sublethal concentrations of microcystin-LR in the onset of cytotoxicity was negligible. Therefore, inhibition of microcystin-LR uptake and the pathway other than ROS production would be involved in the effect of naringin on the attenuation of microcystin-LR toxicity.
Keywords
3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromidePVDFpNPPMC-LROATPOATP1B1OATP1B3IC50FCSVmaxMTTp-nitrophenyl phosphateROSstandard deviationminimum essential mediummaximum velocitypolyvinylidene difluoridefetal calf serumDetoxificationMEMMichaelis constantmicrocystin-LRNaringinhalf maximal inhibitory concentrationProtein phosphataseOrganic anion transporting polypeptideReactive oxygen species
Related Topics
Life Sciences
Environmental Science
Health, Toxicology and Mutagenesis
Authors
Shota Takumi, Satoshi Ikema, Tamami Hanyu, Yusuke Shima, Takashi Kurimoto, Kazuhiro Shiozaki, Yasumasa Sugiyama, Ho-Dong Park, Seiichi Ando, Tatsuhiko Furukawa, Masaharu Komatsu,