Effect of phytochemical (methyl gallate) on nephrotoxicity of cadmium in cultured mouse mesangial cells

초록

To clarify the effect of a phytochemical, methyl gallate (MG) on a heavy metal (cadmium)-induced renal toxicity, cytotoxicity and the change of heme oxygenase-1 (HO-1) gene expression was studied using cultured mouse renal glomerular mesangial cells (MMC). By employing RT-PCR and Western blotting techniques, we have examined the HO-1 induction in MMCs that were treated with Cd or MG and using a cell viability assay (MTT assay), we have also examined the cytoprotective effect of HO-1 induction against the cytotoxicity caused by toxic dose of Cd. In MMCs exposed to Cd and MG, expression of HO-1 (mRNA and protein) was increased in a dose- and time-dependent manner. The up-regulation of HO-1 mRNA and protein expressions by Cd and MG was inhibited by a pre-incubation of the cells with actinomycin D, an inhibitor of mRNA transcription. Upon the inhibition of elevated HO-1 mRNA and protein expressions by the use of zinc protoporphyrin IX (ZnPP), an inhibitor of HO-1 activity, the change of HO-1 mRNA and protein expressions by ZnPP was not observed. The decreased viability of the cells by Cd was partially recovered by the treatment with MG. These cytotoxic and cytoprotective effect was dramatically decreased by the treatment with ZnPP. From these results, methyl gallate have cytoprotective effect that related with heme oxygenase-1 activity.