Abstract
The present study was to investigate the interactions of chitosan derivatives including quaternized chitosan (QC), N‐benzyl‐N,O‐succinyl chitosan (BSCS), N‐naphthyl‐N,O‐succinyl chitosan (NSCS) and N‐octyl‐N,O‐succinyl chitosan (OSCS), with organic cation transporter 1 (OCT1) and OCT2. The transport function of OCT1 and OCT2 was monitored by measurement accumulation of radiolabeled methyl‐4‐phenylpyridinium acetate (3H‐MPP+) in OCT1 and OCT2 heterologous expressing cell and endogenous expressing cells (HepG2 cells and human renal proximal tubular; RPTEC/TERT1 cells). The results revealed that of BSCS, NSCS and OSCS at concentration of 1,000 μg/ml significantly reduced 3H‐MPP+ cellular accumulation compared with control whereas QC showed no effect on OCT1 or OCT2‐mediated 3H‐MPP+ accumulation. Among the chitosan derivatives, OSCS showed the highest inhibitory potency (for OCT1; IC50 = 395±1.10 μg/ml, for OCT2; IC50 = 1,241±1.22 μg/ml). BSCS, NSCS and OSCS significantly reduced maximal transport (Jmax) of OCT1 whereas they increased Kt of OCT2 indicating these compounds inhibited OCT1 and OCT2 transport function by non‐competitive and competitive binding mechanism, respectively. In addition, OSCS significantly reduced 3H‐MPP+ accumulation in HepG2 cells and RPTEC/TERT1 cells with the inhibitory potency of 1,208±1.09 μg/ml and 1,529±1.11 μg/ml, respectively. These results suggested that OSCS may alter OCT1‐ and OCT2‐mediated cationic drug clearances.Support or Funding InformationThis research was supported by the Commission of Higher Education (Thailand), the Thailand Research Fund (TRF) through the Royal Golden Jubilee Ph.D. Program (Grant No.PHD/0139/2557), the TRF through the Natural product‐based drug discovery and development (Grant No. IRN58W0004), Mahidol University (Thailand). The authors would like to thank Prof. Stephen H. Wright for providing rbOCTs‐CHO‐K1 cells.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
