Effect of long-term treatment of trivalent chromium on PPARγ and erythropoietin production in HepG2 cells

<p>Trivalent chromium (Cr) is also used as a supplement and taken for a long period of time. However, there is no consensus on its efficacy, and the effects of long-term treatment are not well understood. We previously reported that Cr treatment for 24 hours increased PPARγ, promoted erythropoietin (EPO) production, and blocked the acquisition of insulin resistance in HepG2 cells. However, the effects of long-term Cr exposure on PPARγ and EPO production in HepG2 cells are unclear. Therefore, in this study, we analyzed the effects on PPARγ and EPO production in HepG2 cells that were passaged while being exposed to Cr for more than 4 weeks. Cr treatment up to 8 weeks maintained significantly high PPARγ mRNA expression levels. The EPO mRNA expression level was also maintained significantly high until 8 weeks. After 4 weeks of Cr treatment, the response to EPO production stimulation by hypoxia and cobalt addition was lower than that of no treatment. Administration of lipopolysaccharide (LPS) to Cr-treated cells for 4 weeks suppressed the increase in EPO mRNA expression compared to untreated cells. Pyocyanin-induced oxidative stress also promoted EPO production, but its effect was attenuated in Cr-treated cells. Inhibition of PPARγ suppressed EPO mRNA expression in Cr-treated cells. These results suggested that the increase in PPARγ and EPO production were sustained in Cr long-term treatment. It was suggested that the enhancement of PPARγ action also enhances EPO production, but the responsiveness to the increase in EPO production due to LPS and oxidative stress is reduced.</p>