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Food Chem Toxicol. 2011 Aug;49(8):1787-95. doi: 10.1016/j.fct.2011.04.028. Epub 2011 May 1.

Preferential binding of insecticide phorate with sub-domain IIA of human serum albumin induces protein damage and its toxicological significance.

Author information

1
A.R. Al-Jeraisy Chair for DNA Research, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.

Abstract

Phorate, an organophosphorus insecticide is known for its adverse effects on acetylcholinesterase, and other neuronal and pulmonary activities. Most likely, the toxicity of drugs/agrochemicals is modulated through cellular distribution bound to plasma proteins. Therefore, the in vitro interaction of phorate with human serum albumin (HSA) has been investigated, using sensitive techniques like fluorescence spectroscopy and circular dichroism, to ascertain its binding mechanism and toxicological implications. Fluorescence studies revealed the quenching constant (Ksv) as 2.5 × 10⁴ M⁻¹ and binding affinity (Ka) as 2.96 × 10⁴ M⁻¹ (r² = 0.99), with a primary binding site of phorate at sub-domain IIA of HSA. Circular dichroism (CD) data demonstrated a noticeable reduction in secondary structure (α-helical content) of phorate treated HSA. Albumin treated with 200-1000 μM phorate released significant amounts of acid soluble amino and carbonyl groups, whereas higher concentrations resulted in protein fragmentation. It is postulated that the 1'-O and 3-O alkyl groups of phorate have a role in binding with electrophilic centers of Trp 214, and Arg 218/Lys 195, respectively. Moreover, the significant ultrastructural changes, reactive oxygen species (ROS) generation, mitochondrial damage and cell death in phorate treated cultured human amnion epithelial (WISH) cells, elucidated phorate induced cellular toxicity.

PMID:
21557983
DOI:
10.1016/j.fct.2011.04.028
[Indexed for MEDLINE]

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