Fluorescence spectroscopic investigation of competitive interactions between ochratoxin A and 13 drug molecules for binding to human serum albumin |
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Authors: | Miklós Poór Sándor Kunsági‐Máté Zsuzsanna Czibulya Yin Li Beáta Peles‐Lemli József Petrik Sanda Vladimir‐Knežević Tamás Kőszegi |
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Institution: | 1. Institute of Laboratory Medicine, University of Pécs, , H‐7624 Pécs, Hungary;2. Department of General and Physical Chemistry, University of Pécs, , H‐7624 Pécs, Hungary;3. János Szentágothai Research Center, , H‐7624 Pécs, Hungary;4. Department of Medical Biochemistry and Haematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, , HR‐10000 Zagreb, Croatia;5. Department of Pharmacognosy, Faculty of Pharmacy and Biochemistry, University of Zagreb, , HR‐10000 Zagreb, Croatia |
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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. Copyright © 2012 John Wiley & Sons, Ltd. |
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Keywords: | competitive interaction drug molecules fluorescence polarization human serum albumin ochratoxin A |
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