In Vitro Inhibition of Three Different Drugs Used in Rheumatoid Arthritis Treatment on Human Serum Paraoxanase 1 Enzyme Activity


DİLEK E., POLAT M.

PROTEIN AND PEPTIDE LETTERS, vol.23, no.1, pp.3-8, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 23 Issue: 1
  • Publication Date: 2016
  • Doi Number: 10.2174/0929866522666151013130102
  • Journal Name: PROTEIN AND PEPTIDE LETTERS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.3-8
  • Erzincan Binali Yildirim University Affiliated: Yes

Abstract

We studied in vitro effects of three different drugs ( ibuprofen, meloxicam and methotrexate) which are often used in rheumatoid arthritis ( RA) treatment on human serum paraoxanase1 (PON1) enzyme activity. The drugs used in RA treatment decreased the in vitro PON1 activity. The inhibition mechanism of ibuprofen and methotrexate were noncompetitive whereas meloxicam was a competitive inhibitor. The IC50 values for ibuprofen, meloxicam and methotrexate were calculated to be 0.35 mM, 0.10 mM, and 0.18 mM, respectively, and the K-i constants were calculated to be 0.890 mM, 0.125 mM, and 0.260 mM, respectively. The IC50 and K-i values showed the maximum inhibition of meloxicam drugs. We propose a prediction scheme for the interaction of meloxicam with the PON1 active site because we thought that meloxicam interacts with the amino acids which are in the PON1 enzyme active site. The results we found showed that these drugs which are often used in RA treatment in vitro inhibit the activity of the enzyme with different inhibition mechanisms at low doses.