Binding of the veterinary drug tetracycline to bovine hemoglobin and toxicological implications

Abstract

Tetracycline (TC) is a widely used veterinary drug in animal breeding and fishery. Because of its low bioavailability, the TC residue extensively exists in the environment (e.g. soils, lakes and rivers), which can enter the human body, being potentially harmful. Hemoglobin (Hb) is a protein responsible for oxygen carrying in the vascular system of animals. The aim of this study was to investigate the interaction of bovine hemoglobin (BHb) with TC through spectroscopic and molecular modeling methods. The experimental results revealed that TC can interact with BHb with one binding site to form a TC-BHb complex, mainly through van der Waals interactions and hydrogen bonds. The UV-visible absorption, synchronous fluorescence, and circular dichroism (CD) results revealed that the binding of TC can cause conformational and some microenvironmental changes of BHb, which may affect BHb physiological functions. The synchronous fluorescence experiment disclosed that TC binds into BHb central cavity, which was verified by molecular modeling study. The work contributes to clarify the molecular mechanism of TC toxicity in vivo.

Keywords:

• Hemoglobin
• veterinary drug residue
• multispectroscopic techniques
• molecular modeling
• toxicity evaluation

Additional information

Funding

This work was supported by State Key Laboratory of Urban Water Resource and Environment, HIT (2013DX09), China Postdoctoral Science Foundation funded project (2013M540297), Natural Scientific Research Innovation Foundation in Harbin Institute of Technology (HIT.NSRIF.2014126), NSFC (21277081), the Cultivation Fund of the Key Scientific and Technical Innovation Project, Ministry of Education of China (708058), Independent innovation program of Jinan (201202083) and Independent innovation foundation of Shandong University natural science projects (2012DX002) are also acknowledged.