title: 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.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, Cheonan, Chungnam 330-090, South Korea.
authors.forename: Tamanna
authors.initials: T
authors.lastname: Zerin
authors.forename: Yong-Sik
authors.initials: YS
authors.lastname: Kim
authors.forename: Sae-Yong
authors.initials: SY
authors.lastname: Hong
authors.forename: Ho-Yeon
authors.initials: HY
authors.lastname: Song
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006540:Herbicides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D006801:Humans; D008775:Methylprednisolone / Q000494:pharmacology*; D010269:Paraquat / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005938:Glucocorticoids; D006540:Herbicides; D010269:Paraquat; D008775:Methylprednisolone