scholarly journals Role of antioxidants in electro catalysis of cytochrome P450 3A4

2014 ◽  
Vol 60 (2) ◽  
pp. 224-234 ◽  
Author(s):  
V.V. Shumyantseva ◽  
A.A. Makhova ◽  
T.V. Bulko ◽  
E.V. Shich ◽  
V.G. Kukes ◽  
...  

The electrochemical analysis of cytochrome Р450 3А4 catalytic activity has shown that vitamins C, A and Е influence on electron transfer and Fe3+/Fe2+ reduction process of cytochrome Р450 3А4. These data allow to assume possibility of cross effects and interference of vitamins-antioxidants with drugs metabolised by cytochrome Р450 3А4, at carrying out of complex therapy. This class of vitamins shows antioxidant properties that lead to increase of the cathodic current corresponding to heme reduction of this functionally significant haemoprotein. Ascorbic acid of 0.028-0.56 mM concentration stimulates cathodic peak (an electrochemical signal) of cytochrome Р450 3А4. At the presence of diclofenac (Voltaren) - a typical substrate of cytochrome Р450 3А4 - the increase growth of a catalytic current testifying to an electrocatalysis and stimulating action of ascorbic acid is observed. In the presence of vitamins A and Е also is registered dose-dependent (in a range of 10-100 M) increase in a catalytic current of cytochrome Р450 3А4: the maximum increase corresponds to 229 ± 20% for 100 M of vitamin A, and 162±10% for 100 M of vitamin E. Vitamin E in the presence of P450’s inhibitor itraconazole doesn't give essential increase in a reductive current, unlike retinol (vitamin A). This effect can manifest substrate properties of tocopherol (vitamin E). The electrochemical approach for the analysis of catalytic activity of cytochrome Р450 3А4 and studies of influence of biologically active compounds on an electrocatalysis is the sensitive and effective sensor approach, allowing to use low concentration of protein on an electrode (till 10-15 mol/electrode), to carry out the analysis without participation of protein redox partners, and to reveal drug-drug or drug-vitamins interaction in pre-clinical experiments.

2020 ◽  
Vol 3 (2) ◽  
pp. 30-35
Author(s):  
S. O. Usenko ◽  
A. M. Shostya ◽  
V. G. Stoyanovskyy ◽  
V. S. Tenditnyk ◽  
G. O. Birta ◽  
...  

The intensity of reproduction of the live-stock of pigs largely depends on environmental factors, in particular fluctuations in indoor temperature, which is often seasonal. It was found out the fact that in the summer with a long rise in temperature it is worsened the quality of sperm in boars, which is accompanied by a decrease in the fertility of sperm, and in multiplicity and large foetus fertility of sows. The aim of the study was to determine the influence of antioxidant vitamins on the prooxidant-antioxidant homeostasis in  blood of boars under the conditions of heat stress. In the study it was used the adult boars of the Large White breed. The duration of the experiment was 120 days, including: preparatory one is 30 days, basic one is 60 days (feeding vitamin A, vitamin E, ascorbic acid) and final one is 30 days. In the main period of the experiment, the diet of animals in the control group remained unchanged, and it was for  two experimental ones with the addition of vitamin A, vitamin E and ascorbic acid. The level of biologically active components in the diet of the experimental groups was higher by 10 % and 20 % compared with the control group. In the received blood samples it has been  determined  the state of prooxidant-antioxidant state. It has been determined that housing boars in conditions of increased temperature is accompanied by the acceleration of peroxidation processes and the depletion of the antioxidant defense system in  blood. The introduction of a vitamin supplement in the feed mixture to boars significantly changes the state of prooxidant-antioxidant homeostasis in this tissue depending on the amount of additionally fed vitamins with antioxidant action. The addition of these biologically active substances by 10 % above the norm after 60 days of feeding increases the content of vitamin A (P < 0.05), vitamin E (P < 0.05), reduced glutathione and slows down the processes of peroxidation – reducing the concentration of diene conjugates (P < 0.01) and TBA-active complexes. Feeding vitamins with antioxidant action in the feed mixture is 20 % more than the norm for boars, compared with the control group, after a month of the use, inhibits peroxidation processes. Two months of using  these compounds probably reduced the number of diene conjugates (P < 0.01) and TBA-active complexes. It is accompanied by an increase in the content of low molecular weight antioxidants – vitamin A (P < 0.01), vitamin E (P < 0.05) and ascorbic acid, the level of which is maintained for at least a month after their use.


2001 ◽  
Vol 85 (05) ◽  
pp. 758-760 ◽  
Author(s):  
Roberto Marchioli

SummaryInterest in the use of antioxidants for the treatment of human disease, and in the role of dietary antioxidants in the prevention of disease development, has been sustained for at least two decades. Several anti-oxidant protective mechanisms exist and constitute a primary defensive system including enzymatic defences (glutathione peroxidase and superoxide dismutase, which depend on the presence of ions such as selenium, zinc, copper, and manganese) and naturally occurring vita-mins such as vitamin E, vitamin A, beta-carotene, and vitamin C. The most important natural antioxidants are vitamin E (in the form of α-, β-, γ-, and δ-tocopherols), beta-carotene, vitamin C and selenium (fundamental constituent of glutathione-peroxidase, i.e., an enzyme with antioxidant function). The first two are lipophilic substances whilst ascorbic acid is hydrophilic. Each antioxidant has a different important mechanism of action since oxidative damage can be caused by lipid- or water-soluble molecules. Lipid-soluble antioxidants are likely to be very important in preventing the peroxidation of low-density lipo-proteins (LDL) and this action could be paramount in the prevention of atherosclerosis. On the other hand, water-soluble antioxidants could be useful where a water-soluble oxidative stress occurs (e.g., inflammation). As lipophilic molecules, vitamin E and beta-carotene are incorporated into the LDL particle. Vitamin E is the main lipid-soluble chain-breaking antioxidant in plasma and tissues and converts the peroxyl-free radical to hydroperoxide, a less reactive radical. It acts as a first-line anti-oxidative defence of LDL particles, protecting unsatu-rated fatty acids from peroxidation. Beta-carotene is a carotenoid (precursor of vitamin A, pro-vitamin) that acts as scavenger of oxidising radicals such as singlet oxygen and is a second-line antioxidative defence of LDL cholesterol. Vitamin C (ascorbic acid) can react with singlet oxygen, superoxide, hydroxyl radicals, and is the first line of antioxi-dative defence in water-soluble compartments. In addition, it plays an important role in regenerating reduced -tocopherol.


2016 ◽  
Vol 24 (2) ◽  
Author(s):  
D. Serova ◽  
O. Taran ◽  
O. Dyomshina

One important reason for non-use of medicinal drugs is their hepatotoxicity. The search for new natural biologically active substances with hepatoprotective properties and which are cost-effective is an important task today. This article presents the data on the impact of the fodder-dietary supplement Humilid alone and in combination with ascorbic acid, and Eco-Impulse on the liver of Mongolian gerbils (Meriones unguiculatus Milne-Edwards, 1867). Hepatomodulation of properties of humic substances in the Humilid confirmed that stimulation of the activity of the enzyme transaminase increases the total amount of protein, especially in combination with ascorbic acid. There was inhibition of accumulation of oxidized products in the cell due to activation of catalase and superoxidedismutase. Intensification of catalase is regarded as one of the important mechanisms of adaptation of the cell under the influence of xenobiotics. Addition of ascorbic acid to the solution Humilid increased the antioxidant action of its active ingredients both through its own antioxidant properties and protection of humic acids from oxidation. Formation of response in liver cells of gerbils receiving active ingredients of the drug Eco-Impulse was accompanied by an increase in the number of TBA-active products and cytochrome C, which indicates the development of oxidative stress, which is accompanied by increased permeability of mitochondrial membranes. The results indicate the hepatoprotective properties of the active ingredients of the drug Humilid, alone and in combination with ascorbic acid, and the need for correcting the concentration of the drug Eco-Impulse for use in clinical practice. 


2016 ◽  
Vol 24 (2) ◽  
pp. 109-118 ◽  
Author(s):  
Irina Burdina ◽  
Olesia Priss

AbstractBasil (Ocimum basilicumL.) is an aromatic herb which has a high value and is of high demand in the world. Basil in Ukraine is grown mainly in small farms and country house gardens. The influence of the substrate composition (proportions of peat to perlite) on the yield of herbs and on the accumulation of biologically active substances with antioxidant properties was studied for two cultivars grown in a green-house. It was found that the substrate composition influenced the fresh and dry weight, as well as level of total phenolic compounds, carotenoids and essential oils of basil. The herbs yield, ascorbic acid and essential oils concentration increased at an addition of 20, 40 and 60% of perlite, and decreased at 80% as compared to 100% peat. Plants of both cultivars accumulated the highest amount of phenolic substances when grown in the substrate, which contained 40% of peat and 60% of perlite. The concentration of ascorbic acid increased in plants grown in the substrates with 20, 40 and 60% of perlite, mostly at 40%. Significant increase in the concentration of carotenoids differed for cultivars and in ʽBad’oryi’ cv. increased at 20 and 40% perlite, but in ʽFilosof’ at 20, 40 and 60%.


Author(s):  
K.N. Bushmeleva ◽  
A.B. Vyshtakalyuk ◽  
D.A. Terenzhev ◽  
E.N. Nikitin

Background: Coniferous tree species typical of the central part of Russia can be evaluated not only as sources of wood but also as a raw material for obtaining biologically active substances.Methods: A comparative evaluation of needle juices of Pinus sylvestris and Picea abies in the summer and winter periods was the objective of this study and carried out in this study by chemiluminescence analysis and testing for membrane-protective activity. Juices were evaluated for the content of flavonoids and ascorbic acid, which some authors suggest are markers of stress in plants. An increase in the content of flavonoids and ascorbic acid in Pinus sylvestris L. in the summer period is a sign of an adaptive reaction of plants to the high intensity of ultraviolet radiation, which is typical for the growing conditions of pine as a photophilous plant. An increase in these indicators in Picea abies L. in winter is a sign of the plant stress response to low temperatures. Result: The membrane-protective activity of needle juices concerning peroxidation and osmotic hemolysis was revealed, which is more prominent in Pinus sylvestris L. needle juice. The analysis revealed more prominent antioxidant properties in the juice of Pinus sylvestris L. needles compared to that of Picea abies L. both in summer and in winter.


2000 ◽  
Vol 59 (4) ◽  
pp. 587-594 ◽  
Author(s):  
Jerry W. Spears

Complex inter-relationships exist between certain micronutrients, immune function and disease resistance in cattle. Several micronutrients have been shown to influence immune responses. The relationship between deficiencies of some micronutrients and disease resistance is less clear. A number of studies have indicated that Cr supplementation may improve cell-mediated and humoral immune response as well as resistance to respiratory infections in stressed cattle. With respiratory-disease challenge models Cr generally does not affect disease resistance. Deficiencies of Cu, Se, vitamin E and Co in cattle reduce the ability of isolated neutrophils to kill yeast and/or bacteria. Cu deficiency reduces antibody production, but cell-mediated immunity is generally not altered. However, Cu deficiency appears to reduce production of interferon and tumour necrosis factor by mononuclear cells. Numerous studies have linked low vitamin E and/or Se status to increased susceptibility of dairy cows to intramammary infections. In contrast to findings in laboratory animals, marginal Zn deficiency does not appear to impair antibody production or lymphocyte responsiveness to mitogen stimulation in ruminants. Co deficiency has been associated with reduced resistance to parasitic infections. It is well documented that vitamin A-deficient animals are more susceptible to various types of infections. β-Carotene, possibly via its antioxidant properties, may affect immune function and disease resistance independent of its role as a precursor of vitamin A.


Author(s):  
V. G. Stoianovskyi ◽  
S. O. Usenko ◽  
A. M. Shostya ◽  
V. М. Sokolenko ◽  
K. Ye. Yudina ◽  
...  

The peculiarities of formation of prooxidant-antioxidant homeostasis (PAG) in boars of different types of higher nervous activity have been studied. Using motor-nutritional techniques, it has been opposed adult boars of the Large White breed aged 24–36 months according to the main types of higher nervous activity (HNA). Four groups of 3 heads each were formed. The first group includes animals of a strong balanced lively (mobile) type; group II includes a strong balanced calm (inert) type; group III includes a strong unbalanced (unrestrained) type; group IV includes a weak type of higher nervous activity. Sperm was received from boars manually, taking into account the total time of ejaculation, dividing the ejaculate into 4 fractions – F1 – the first, F2 – the second, F3 – the third, F4 – the fourth. PAGs in blood and ejaculates of boars were evaluated by the intensity of peroxidation processes (xanthine oxidase, diene conjugates, TBA-active compounds) and antioxidant defense systems (superoxide dismutase, catalase, reduced glutathione, ascorbic acid, vitamin A and vitamin E). Sperm contained higher amounts of diene conjugates and TBA-active complexes (P < 0.05) compared to blood. The second tissue relative to the first one is characterized by a higher level of antioxidant defense: catalase activity, concentration of ascorbic acid, vitamin A and vitamin E. The process of PAG formation in the tissues of boars depends on the type of higher nervous activity (HNA). Thus, in individuals of a strong balanced lively and calm type, the course of peroxidation processes is somewhat slower because of a lower concentration of diene conjugates and TBA-active complexes. It was determined the fact that in blood and sperm of boars of strong unbalanced and weak types of HNA the course of peroxidation is more intense, the antioxidant defense system is at a lower level that is connected with less superoxide dismutase activity (P < 0.05), concentration of ascorbic acid (P < 0.001), vitamin A (P < 0.01–0.001), and vitamin E (P < 0.001). In the second and third fractions of ejaculate of boars, the PAG is shifted in the direction of probable acceleration of peroxidation processes, especially in strong unbalanced and weak types of HNA because of a higher concentration of diene conjugates, dehydroascorbic acid. Animals of a strong balanced lively and calm types of HNA are characterized by a higher level of antioxidant defence – catalase activity, superoxide dismutase, reduced glutathione, ascorbic acid and vitamin E. In the first and fourth fractions of ejaculate, peroxidation processes are slower and there is no superoxide dismutase activity and the amount of vitamin A and vitamin E.


Author(s):  
Anna A. Makhova ◽  
Eugenia V. Shikh ◽  
Tatiana V. Bulko ◽  
Zhanna M. Sizova ◽  
Victoria V. Shumyantseva

Abstract Background Cytochrome P450s (CYPs, EC 1.14.14.1) are the main enzymes of drug metabolism. The functional significance of CYPs also includes the metabolism of foreign chemicals and endogenic biologically active compounds. The CYP3A4 isoform contributes to the metabolism of about half of all marketed medicinal preparations. The aim of this study was to investigate the effects of two biologically active compounds: 2-aminoethane-sulfonic acid (taurine) and 3-hydroxy-4-trimethylaminobutyrate (L-carnitine) on urinary 6β-hydroxycortisol/cortisol (6β-OHC/cortisol) metabolic ratio as a biomarker of the CYP3A4 activity of healthy volunteers. Taurine is used for the treatment of chronic heart failure and liver disease. Cardiologists, nephrologists, neurologists, gerontologists in addition to the main etiopathogenetic therapies, use L-carnitine. The quantification of the 6β-OHC/cortisol metabolic ratio as a biomarker of CYP3A4 activity in human urine was used for the assessment of CYP3A4 catalytic activity as a non-invasive test. Methods The study included 18 healthy male volunteers (aged from 18 to 35 years old). The volunteers took taurine in a dose of 500 mg twice a day or L-carnitine in a dose of 2.5 mL 3 times a day for 14 consecutive days. The test drug was given 20 min before meals. The collection of urine samples was performed before and after 3, 7, 10, and 14 days after taurine intake. The metabolic ratio of 6β-OHC/cortisol in morning spot urine samples was studied by the liquid chromatography/mass spectroscopy (LC/MS) method. Results The ratio of 6-6β-OHC/cortisol was used as a biomarker to study the taurine and L-carnitine influence on CYP3A4 metabolism of cortisol. The ratio of urinary 6β-OCH/cortisol in the morning urine samples of volunteers before the beginning of taurine therapy (baseline ratio) was 2.71 ± 0.2. Seven days after the administration of taurine in a dose of 500 mg twice a day, the 6β-OCH/cortisol ratio was 3.3 ± 0.2, which indicated the increased catalytic activity of CYP3A4 towards cortisol. As for the L-carnitine supplementation, analysis of the 6β-OCH/cortisol ratio in the urine for 14 days did not show any significant changes in this baseline ratio, indicating the lack of L-carnitine influence on the catalytic activity of CYP3A4 to cortisol. Conclusions The results obtained demonstrated the influence of taurine on 6β-OCH/cortisol metabolic ratio as a biomarker of CYP3A4 catalytic activity to cortisol. L-carnitine did not affect the activity of CYP3A4. The lack of a clinically meaningful effect of L-carnitine was established.


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