Polyphenols of Mangifera indica modulate arsenite-induced cytotoxicity in a human proximal tubule cell line

Inorganic arsenic is an ubiquitous environmental contaminant able to cause severe pathologies in humans, including kidney disorders. The possible protective effects of Mangifera indica L., Anacardiaceae, stem bark extract (MSBE) and some mango phenols on the cytotoxicity of arsenite (AsIII) in the proximal tubule cell line HK-2 was investigated. In cells cultured for 24 h in presence of AsIII, a dose-dependent loss of cell viability occurred that was significantly alleviated by MSBE, followed by gallic acid, catechin and mangiferin. Mangiferin complexed with Fe+++ proved more efficacious than mangiferin alone. MSBE and pure phenols increased significantly the cell surviving fraction in clonogenic assays. In cells pretreated with MSBE or phenols for 72 h the protection afforded by MSBE resulted decreased in comparison with the shorter experiments. Cells pretreated with a subcytotoxic amount of AsIII or cultured in continuous presence of low concentration of mangiferin proved to be more resistant to AsIII, while cells cultured in presence of albumin resulted more sensitive. Because all the above conditions share changes in expression/activity of P-glycoprotein (P-gp), a transporter potentially involved in arsenic resistance, the capability of M. indica phenols in modulating AsIII-induced cytotoxicity would be at least in part dependent on their interactions with P-gp.