Protective effect of methylprednisolone on paraquat-induced A549 cell cytotoxicity via induction of efflux transporter, P-glycoprotein expression

Abstract

Paraquat (PQ) is the third most extensively used herbicide in the world, causing thousands of deaths due to accidental or intentional self-poisoning in developing countries. Although many therapeutic treatments for PQ-induced poisonings have been proposed and developed, the efficacy of these treatments is still poor and requires further investigation. Methylprednisolone (trade name Solumedrol, hereinafter MP) is a widely used steroid for the treatment of various diseases but the function of MP has not yet been studied in the context of PQ-induced intoxication. The aim of this study was to determine if MP can ameliorate PQ-induced toxicity in an alveolar A549 cell line by inducing ATP-dependent transporter P-glycoprotein (P-gp) expression. P-gp expression and activity in the PQ-treated A549 cell line were enhanced by MP treatment and cytotoxicity by PQ was dramatically decreased. We also found that MP per se or together with PQ induced P-gp expression by both Western blot and qRT-PCR analyses. In addition, induced P-gp transporter was shown to improve the efflux effect on PQ-treated A549 cell lines as was demonstrated using the Calcein-AM fluorescence accumulation assay. In summary, MP induces the transmembrane ATP-dependent transporter P-gp expression, which greatly improves PQ-treated A549 cell viability, reduces accumulation of intracellular PQ and prevents PQ induced cytotoxicity but it should be further evaluated in in vivo studies. (C) 2011 Elsevier Ireland Ltd. All rights reserved.