title: Fluorescence spectroscopic investigation of competitive interactions between ochratoxin A and 13 drug molecules for binding to human serum albumin.
abstract: Ochratoxin A (OTA) is a highly toxic mycotoxin found worldwide in cereals, foods, animal feeds and different drinks. Based on previous studies, OTA is one of the major causes of the chronic tubulointerstitial nephropathy known as Balkan endemic nephropathy (BEN) and exerts several other adverse effects shown by cell and/or animal models. It is a well-known fact that OTA binds to various albumins with very high affinity. Recently, a few studies suggested that reducing the bound fraction of OTA might reduce its toxicity. Hypothetically, certain drugs can be effective competitors displacing OTA from its albumin complex. Therefore, we examined 13 different drug molecules to determine their competing abilities to displace OTA from human serum albumin (HSA). Competitors and ineffective chemicals were identified with a steady-state fluorescence polarization-based method. After characterization the competitive abilities of individual drugs, drug pairs were formed and their displacing activity were tested in OTA-HSA system. Indometacin, phenylbutazone, warfarin and furosemide showed the highest competing capacity but ibuprofen, glipizide and simvastatin represented detectable interaction too. Investigations of drug pairs raised the possibility of the presence of diverse binding sites of competing drugs. Apart from the chemical information obtained in our model, this explorative research might initiate future designs for epidemiologic studies to gain further in vivo evidence of long-term (potentially protective) effects of competing drugs administered to human patients.
authors.affiliation: Institute of Laboratory Medicine, University of Pécs, H-7624, Pécs, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Poór
authors.forename: Sándor
authors.initials: S
authors.lastname: Kunsági-Máté
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Czibulya
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.forename: Beáta
authors.initials: B
authors.lastname: Peles-Lemli
authors.forename: József
authors.initials: J
authors.lastname: Petrik
authors.forename: Sanda
authors.initials: S
authors.lastname: Vladimir-Knežević
authors.forename: Tamás
authors.initials: T
authors.lastname: Kőszegi
mesh_terms: D001665:Binding Sites; D006801:Humans; D009793:Ochratoxins / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
chemical_list: D009793:Ochratoxins; D004364:Pharmaceutical Preparations; D012709:Serum Albumin; C025589:ochratoxin A