Heme oxygenase-1 mediated protective effect of methyl gallate on cadmium-induced cytotoxicity in cultured mouse mesangial cells

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 analysis, we have examined the HO-1 induction in MMCs that were treated with Cd2+ and/or MG. Using MTT assay we have also examined the cytoprotective effect of HO-1 induction against the cytotoxicity caused by toxic dose of Cd2+. In MMCs exposed to Cd2+ and MG, expression of HO-1 (mRNA and protein) was increased in a concentration- and time-dependent manner. The increments of HO-1 mRNA and protein expressions by Cd2+ and MG were inhibited by the treatment of the cells with actinomycin D, an inhibitor of transcription. The decreased viability of the cells by Cd2+ was partially recovered by the treatment of MG and this recovery by the MG was reduced by the treatment of zinc protoporphyrin IX (a HO-1 inhibitor). From these results, methyl gallate might have cytoprotective effect on Cd2+-induced cytotoxicity that is related with heme oxygenase-1 induction.