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. [Copyright &y& Elsevier]