scholarly journals Electroanalytical and electrocatalytical characteristics of cytochrome P450 3A4 using electrodes modified with nanocomposite carbon nanomaterials

2020 ◽  
Vol 66 (1) ◽  
pp. 64-70 ◽  
Author(s):  
A.V. Kuzikov ◽  
T.V. Bulko ◽  
P.I. Koroleva ◽  
R.A. Masamrekh ◽  
S.S. Babkina ◽  
...  

The electroanalytical characteristics of recombinant cytochrome P450 3A4 (P450 3A4) immobilized on the surface of screen-printed graphite electrodes modified with multi-walled carbon nanotubes have been studied. The role and the influence of graphite working electrode modification with carbon nanotubes on electroanalytical characteristics of cytochrome P450 3A4 have been demonstrated. The conditions for the immobilization of cytochrome P450 3A4 on the obtained screen-printed graphite electrodes modified with carbon multi-walled nanotubes have been optimized. The electrochemical parameters of the oxidation and reduction of the heme iron of the enzyme have been estimated. The midpoint potential E0′ was -0.35±0.01 V vs Ag/AgCl; the calculated heterogeneous electron transfer rate constant ks, was 0.57±0.04 s-1; the amount of electroactive cytochrome P450 3A4 on the electrode Г0, was determined as (2.6±0.6)⋅10-10 mol/cm2. The functioning mechanism of P450 3A4-based electrochemical sensor followed the “protein film voltammetry”. In order to develop electrochemical analysis of drugs being substrates of that hemoprotein and respective medical biosensors the voltammetric study of catalytic activity of immobilized cytochrome P450 3A4 was carried out. Electrocatalytic properties of cytochrome P450 3A4, immobilized on modified screen-printed graphite electrodes, has been investigated using erythromycin (macrolide antibiotics). It has been shown that the modification of electrodes plays a decisive role for the study of the properties of cytochromes P450 in electrochemical investigations. Smart electrodes can serve as sensors for analytical purposes, as well as electrocatalysts for the study of biotransformation processes and metabolic processes. Electrodes modified with carbon nanomaterials are applicable for analytical purposes in the registration of hemoproteins. Electrodes modified with synthetic membrane-like compounds (e.g. didodecyldimethylammonium bromide) are effective in enzyme-dependent electrocatalysis.

2011 ◽  
Vol 57 (3) ◽  
pp. 343-354 ◽  
Author(s):  
V.V. Shumyantseva ◽  
E.V. Shich ◽  
A.A. Machova ◽  
T.V. Bulko ◽  
V.G. Kukes ◽  
...  

It was shown that vitamin B group permit to shorten the longitude of diclofenak therapy and to reduce the daytime dose of this drug. All three schemes of diclofenac treatment - only diclofenac, diclofenac plus 2 tablets of Gitagamp (mixture of vitamin B group), and diclofenac plus 4 tablets of Gitagamp - gave maximum value of diclofenal in blood through 1 hour after treatment. In the case of diclofenak treatment without vitamins Cmax corresponds to 1137.2±82.4 ng/ml, with 2 tablets of Gitagamp - Cmax 1326.7±122.5 ng/ml, and with 4 tablets - Cmax 2200.4±111.3 ng/ml. Positive influence of vitamin B group on the decrease of pain syndrome was shown. Pharmacodynamics and pharmacokinetics data were confirmed in electrochemical experiments with cytochrome P450 3A4. For enzyme immobilization screen printed graphite electrodes modified with gold nanoparticles and synthetic membrane-like compound didodecyldimethylammonium bromide (DDAB/Au) were used. Electrochemical analysis reviled the influence of vitamin B group on metabolism of non steroid anti inflammation drug diclofenac catalyzed by cytochrome P450 3A4. Riboflavin was the most effective inhibitor of diclofenac hydroxylation by cytochrome P450 3A4 as was compared at 300 M concentration of vitamin B group (B1, B2, B6). These data confirmed the opportunity of pharmacokinetic parameters regulation and the level of pharmacodynamic effects by the influence of vitamin B group on the catalytic activity of cytochrome P450 3A4.


2016 ◽  
Vol 77 ◽  
pp. 1168-1174 ◽  
Author(s):  
Naiara Hernández-Ibáñez ◽  
Leticia García-Cruz ◽  
Vicente Montiel ◽  
Christopher W. Foster ◽  
Craig E. Banks ◽  
...  

Sensors ◽  
2022 ◽  
Vol 22 (2) ◽  
pp. 675
Author(s):  
M. Amin ◽  
B. M. Abdullah ◽  
S. J. Rowley-Neale ◽  
S. Wylie ◽  
A. J. Slate ◽  
...  

Carbon nanomaterials have gained significant interest over recent years in the field of electrochemistry, and they may be limited in their use due to issues with their difficulty in dispersion. Enzymes are prime components for detecting biological molecules and enabling electrochemical interactions, but they may also enhance multiwalled carbon nanotube (MWCNT) dispersion. This study evaluated a MWCNT and diamine oxidase enzyme (DAO)-functionalised screen-printed electrode (SPE) to demonstrate improved methods of MWCNT functionalisation and dispersion. MWCNT morphology and dispersion was determined using UV-Vis spectroscopy (UV-Vis) and scanning electron microscopy (SEM). Carboxyl groups were introduced onto the MWCNT surfaces using acid etching. MWCNT functionalisation was carried out using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-Hydroxysuccinimide (NHS), followed by DAO conjugation and glutaraldehyde (GA) crosslinking. Modified C-MWNCT/EDC-NHS/DAO/GA was drop cast onto SPEs. Modified and unmodified electrodes after MWCNT functionalisation were characterised using optical profilometry (roughness), water contact angle measurements (wettability), Raman spectroscopy and energy dispersive X-ray spectroscopy (EDX) (vibrational modes and elemental composition, respectively). The results demonstrated that the addition of the DAO improved MWCNT homogenous dispersion and the solution demonstrated enhanced stability which remained over two days. Drop casting of C-MWCNT/EDC-NHS/DAO/GA onto carbon screen-printed electrodes increased the surface roughness and wettability. UV-Vis, SEM, Raman and EDX analysis determined the presence of carboxylated MWCNT variants from their non-carboxylated counterparts. Electrochemical analysis demonstrated an efficient electron transfer rate process and a diffusion-controlled redox process. The modification of such electrodes may be utilised for the development of biosensors which could be utilised to support a range of healthcare related fields.


2015 ◽  
Vol 27 (9) ◽  
pp. 2230-2238 ◽  
Author(s):  
Stefano Cinti ◽  
Fabiana Arduini ◽  
Marilena Carbone ◽  
Lucia Sansone ◽  
Ilaria Cacciotti ◽  
...  

1995 ◽  
Vol 270 (10) ◽  
pp. 5014-5018 ◽  
Author(s):  
Aditya P. Koley ◽  
Jeroen T. M. Buters ◽  
Richard C. Robinson ◽  
Allen Markowitz ◽  
Fred K. Friedman

2021 ◽  
Vol 22 (12) ◽  
pp. 6480
Author(s):  
Céline K. Stäuble ◽  
Markus L. Lampert ◽  
Thorsten Mikoteit ◽  
Martin Hatzinger ◽  
Kurt E. Hersberger ◽  
...  

We report two cases of patients who developed severe adverse drug reactions including persistent movement disorders, nausea, and vertigo during treatment with quetiapine at maximum daily doses ranging between 300 and 400 mg. The extensive hepatic metabolism of quetiapine is mainly attributed to cytochrome P450 3A4 (CYP3A4). However, there is recent evidence supporting the idea of CYP2D6 playing a role in the clearance of the quetiapine active metabolite norquetiapine. Interestingly, both patients we are reporting of are carriers of the CYP2D6*4 variant, predicting an intermediate metabolizer phenotype. Additionally, co-medication with a known CYP2D6 inhibitor and renal impairment might have further affected quetiapine pharmacokinetics. The herein reported cases could spark a discussion on the potential impact of a patient’s pharmacogenetic predisposition in the treatment with quetiapine. However, further studies are warranted to promote the adoption of pharmacogenetic testing for the prevention of drug-induced toxicities associated with quetiapine.


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