Binding of pyridostigmine bromide, N,N-diethyl- m-toluamide and permethrin, alone and in combinations, to human serum albumin

Abstract

In this study we examined the interaction of the anti-nerve agent drug pyridostigmine bromide (PB, 3,3-dimethylaminocarbonyloxy- N-methylpyridiniyum bromide), the insect repellent DEET ( N, N-diethyl- m-toluamide), and the insecticide permethrin [3-(2,2-dichloroethyl)-2,2-dimethylcyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester] in binding to human serum albumin (HSA). Concentrations between 500 ng/ml and 10 microg/ml PB, DEET and permethrin, alone or in combination, were incubated with HSA at 37 degrees C for 60 min. Concentrations of PB, DEET and permethrin were determined using high performance liquid chromatography (HPLC). The results showed that 81.2+/-4.2%, and 84.6+/-2.5% of the initial concentration of PB was bound to HSA when incubated alone or in combination with DEET or permethrin, respectively. DEET and permethrin did not significantly interact with HSA after 1 h of incubation. Incubation of combinations of two or three compounds did not significantly alter the binding pattern of any of the compounds with HSA. These results showed that PB is highly bound to albumin protein, while the competition between PB, DEET and permethrin on binding sites of HSA as a possible site of interaction following combined administration in vivo is not likely.

Subacute pyridostigmine exposure increases heart rate recovery and cardiac parasympathetic tone in rats

“…Thus, there may be more stoichiometric binding sites for pyridostigmine in the plasma as compared with the RBCs, and thus less inhibition of AChE in plasma, despite similar concentrations of pyridostigmine. Pyridostigmine may also bind to plasma albumin, decreasing its unbound concentration that is available to inhibit plasma enzymes.…”

Feasibility of Biomonitoring of Exposure to Permethrin Through Analysis of Long-Lived (Metabolite) Adducts to Proteins

“…In our laboratory we developed methods for biomonitoring of exposure to CW agents based on mass spectrometric analysis of such protein adducts, , e.g., adducts of sulfur mustard with hemoglobin and albumin and of adducts of nerve agents with butyrylcholinesterase (for overviews see Black and Noort, 2005. In view of its chemical structure, it should not be expected that permethrin itself will react with proteins to give adducts, as experimentally established for albumin (Abu-Qare and Abou-Donia, 2002). …”

Dual‐opposite multi‐walled carbon nanotube modified carbon fiber microelectrode for microfluidic chip‐capillary electrophoresis determination of methyl parathion metabolites in human urine

“…Because of its high toxicity to humans, the U. S. Environmental Protection Agency (U. S. EPA) has classified MP as a pesticide for restricted use [2]. The serious health effects of MP have aroused public awareness [3][4][5][6], leading to the start of risk assessment of human exposure to MP.…”

“…The collection of urine sample is much easier and less intrusive than collecting blood sample via venipuncture, thus it is preferred to determine the biomarker in urine samples. The biological half-life of MP in animals is 7-17 h [3,7]. After exposure to MP, it is rapidly metabolized in the human body, to produce dimethylthiophosphate (DMTP), dimethylphosphate (DMP), and 4-nitrophenol (4-NP).…”