Structural and Functional Impacts of Albumin Oxidation by Hypochlorite: Possible Changes in Drug Binding Characteristics upon Myeloperoxidase-Mediated Oxidation in Vivo

Mohammad Reza Ashrafi-Kooshk; Reza Khodarahmi; Arash Karimi; Mohammad Reza Nikbakht

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Structural and Functional Impacts of Albumin Oxidation by Hypochlorite: Possible Changes in Drug Binding Characteristics upon Myeloperoxidase-Mediated Oxidation in Vivo

Author(s):

Mohammad Reza Ashrafi-Kooshk¹,

Reza Khodarahmi^1,*,

Arash Karimi²,

Mohammad Reza Nikbakht³

1Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

2Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

3Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

Journal of Reports in Pharmaceutical Sciences:Vol. 1, issue 2; 94-106

Published online:Dec 27, 2012

Article type:Research Article

Received:Nov 11, 2012

Accepted:Dec 23, 2012

How to Cite:Mohammad Reza Ashrafi-KooshkReza KhodarahmiArash KarimiMohammad Reza NikbakhtStructural and Functional Impacts of Albumin Oxidation by Hypochlorite: Possible Changes in Drug Binding Characteristics upon Myeloperoxidase-Mediated Oxidation in Vivo.J Rep Pharm Sci.1(2):e147770.

Abstract

Interaction of drugs with serum albumin, the most abundant protein in plasma, has a great significance in pharmaceutical sciences. It can affect the biological activity, toxicity, and pharmacokinetics of drugs and design of dosages. Determination of the impact of chemical modifications of albumin and its structural changes upon interaction with drugs are very important when drugs bind with albumin to a significant degree. Hypochlorite is naturally produced by activated phagocytes in vivo at inflammatory conditions. In current study, the effects of hypochlorite-mediated oxidation on the albumin stability, surface hydrophobicity and its interaction with furosemide were investigated using intrinsic and extrinsic fluorescence techniques. Bovine serum albumin (BSA) was chemically modified with sodium hypochlorite under nondenaturing conditions. The Job’s plot indicated that the drug binds to the unmodified and modified BSAs with a 1:1 stoichometry. Fluorescence quenching data showed that the albumin affinity for the drug as well as its surface hydrophobicity increases under the effect of protein oxidation. Measurement of conformational stability indicated that oxidized BSA is less stable compared to the unmodified protein. Thermodynamic analyses of the binding process showed that the major forces involved in the interaction of furosemide to the unmodified and oxidized BSA are same (hydrophobic). Increment of protein surface hydrophobicity (PSH) as well as the decrement of protein stability may reminiscent of higher protein structural flexibility upon oxidation which may affect the drug binding site.

Keywords

Bovine Serum Albumin

Furosemide

Binding Site Fluorescence

Quenching

Protein Surface Hydrophobicity

Conformational Stability

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