Effect of Cellgevity® Supplement on Selected Rat Liver Cytochrome P450 Enzyme Activity and Pharmacokinetic Parameters of Carbamazepine

2020 ◽  
Author(s):  
Seth Kwabena Amponsah ◽  
Benoit Banga Nguessan ◽  
Martin Akandawen ◽  
Abigail Aning ◽  
Sedem Yawa Agboli ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Cytochrome P450 ◽  
Rat Liver ◽  
Normal Saline ◽  
Pharmacokinetic Parameters ◽  
Cytochrome P450 Enzyme ◽  
Sprague Dawley ◽  
Serum Samples ◽  
Liver Cytochrome ◽  
Sd Rats

Abstract Background: There is considerable evidence that many patients concurrently administer dietary supplements with conventional drugs, creating a risk for potential drug-supplement interaction. The aim of this study was to determine the effect of Cellgevity® supplement on selected rat liver cytochrome P450 (CYP) enzymes. Also, we sought to deternine the effect of Cellgevity® on the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Methods: Male Sprague-Dawley (SD) rats were randomly put into 5 groups and administered (per os) either distilled water (negative control), Cellgevity® (3 separate doses) or phenobarbital (positive control). Modulation of liver CYP enzyme activity was evaluated after 30 days of treatment, using probe substrates, spectroscopic and high-performance liquid chromatographic methods. In the pharmacokinetic study, 12 SD rats were divided into 2 groups administered (per os) carbamazepine plus Cellgevity®, or carbamazepine plus normal saline, both over a period of 14 days. Blood samples from rats in the same group were collected after treatment. Serum samples were prepared and pooled together at each specific sampling time point. Levels of carbamazepine were determined using a fluorescence polarization immunoassay. Results: Activities of rat liver CYP1A1/2, CYP2C9 and CYP2D6 were significantly increased by Cellgevity® after 30-day treament. Pharmacokinetic parameters for rats administered carbamazepine with Cellgevity® vis-a-vis carbamazepine with normal saline were as follows: Cmax; 20 μmol/L vs 11 μmol/L, AUC0→24; 347 μmol.h/L vs 170 μmol.h/L, Ke; 0.28 h-1 vs 0.41 h-1, and t1/2; 2.3 h vs 1.7 h, respectively.Conclusions: Cellgevity® increased the activity of rat CYP1A1/2, CYP2C9 and CYP2D6 enzymes, and altered the pharmacokinetics of carbamazepine in rats.

Effect Of 30-Day Administration Of Cellgevity® Supplement On Selected Rat Liver Cytochrome P450 Enzyme Activity And Supplement Interaction With Carbamazepine

2019 ◽  
Author(s):  
Seth Kwabena Amponsah ◽  
Benoit Banga Nguessan ◽  
Martin Akandawen ◽  
Abigail Aning ◽  
Sedem Yawa Agboli ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Cytochrome P450 ◽  
Rat Liver ◽  
Normal Saline ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Cytochrome P450 Enzyme ◽  
Sprague Dawley ◽  
Liver Cytochrome ◽  
Sd Rats

Abstract BackgroundThere is considerable evidence that many patients concurrently take dietary supplements with conventional drugs, with a risk of potential drug-supplement interaction. The aim of this study was to determine the effect of Cellgevity® supplement on selected rat liver cytochrome P450 (CYP) enzymes and on the pharmacokinetics of carbamazepine.MethodsSprague-Dawley (SD) rats were put into 5 groups and modulation of CYP enzyme activity by Cellgevity® was determined by comparing the enzyme activity of Cellgevity-treated groups with the negative control group after 30 days of treatment. For the effect of Cellgevity® on the pharmacokinetics of carbamazepine, 12 SD rats were put into 2 groups; one group received an oral administration of carbamazepine plus Cellgevity®, and the other carbamazepine plus normal saline. Blood samples were collected at specific time points and analyzed for levels of carbamazepine. ResultsActivities of CYP1A1/2, CYP2C9 and CYP2D6 were significantly increased by Cellgevity®. The pharmacokinetic parameters for rats administered carbamazepine with Cellgevity® vis-a-vis carbamazepine with normal saline were changed as follows: Cmax; 20 μmol/L vs 11 μmol/L, AUC0→24; 347 μmol.h/L vs 170 μmol.h/L, Ke; 0.28 h-1 vs 0.41 h-1, and t1/2; 2.3 h vs 1.7 h, respectively.ConclusionsCellgevity® increased the activity of rat CYP1A1/2, CYP2C9 and CYP2D6, and also altered the pharmacokinetics of carbamazepine in rats.

scholarly journals Effect of Cellgevity® Supplement on Selected Rat Liver Cytochrome P450 Enzyme Activity and Pharmacokinetic Parameters of Carbamazepine

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Seth Kwabena Amponsah ◽  
Benoit Banga N’guessan ◽  
Martin Akandawen ◽  
Abigail Aning ◽  
Sedem Yawa Agboli ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Cytochrome P450 ◽  
Rat Liver ◽  
Normal Saline ◽  
Day Treatment ◽  
Pharmacokinetic Parameters ◽  
Cytochrome P450 Enzyme ◽  
Sprague Dawley ◽  
Liver Cytochrome ◽  
Sd Rats

Background. There is considerable evidence that many patients concurrently administer dietary supplements with conventional drugs, creating a risk for potential drug-supplement interaction. The aim of this study was to determine the effect of Cellgevity® supplement on selected rat liver cytochrome P450 (CYP) enzymes. Also, based on our previous finding, we sought to determine the effect of Cellgevity® on the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Methods. Male Sprague–Dawley (SD) rats were randomly put into 5 groups and administered either distilled water (negative control), Cellgevity® (3 separate doses), or phenobarbital (positive control), per os. Modulation of liver CYP enzyme activity was evaluated after 30 days of treatment, using probe substrates, spectroscopic, and high-performance liquid chromatographic methods. In the pharmacokinetic study, 12 SD rats were put into 2 groups and administered carbamazepine plus normal saline (group 1) or carbamazepine plus Cellgevity® (group 2), per os, both over a period of 14 days. Blood samples from rats in the same group were collected after treatment. Serum samples were prepared and pooled together at each specific sampling time point. Levels of carbamazepine were determined using a fluorescence polarization immunoassay. Results. Activities of rat liver CYP1A1/2, CYP2C9, and CYP2D6 were significantly increased by Cellgevity® after 30-day treatment. Pharmacokinetic parameters for rats administered carbamazepine with Cellgevity® vis-a-vis carbamazepine with normal saline were as follows: Cmax; 20 μmol/L vs 11 μmol/L, AUC0⟶24; 347 μmol h/L vs 170 μmol h/L, Ke; 0.28 h−1 vs 0.41 h−1, and t1/2; 2.3 h vs 1.7 h, respectively. Conclusions. Cellgevity® increased the activity of rat CYP1A1/2, CYP2C9, and CYP2D6 enzymes and was found to alter the pharmacokinetics of carbamazepine in rats.

In vitro effect of mPEG2k-PCLx micelles on rat liver cytochrome P450 enzymes

2018 ◽  
Vol 552 (1-2) ◽  
pp. 99-110 ◽  
Author(s):  
Lihui Qiu ◽  
Qian Li ◽  
Jiangeng Huang ◽  
Qi Wu ◽  
Kun Tu ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Rat Liver ◽  
Cytochrome P450 Enzymes ◽  
Liver Cytochrome ◽  
Vitro Effect

scholarly journals Acute and Chronic Toxicity, Cytochrome P450 Enzyme Inhibition, and hERG Channel Blockade Studies with a Polyherbal, Ayurvedic Formulation for Inflammation

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Debendranath Dey ◽  
Sunetra Chaskar ◽  
Nitin Athavale ◽  
Deepa Chitre
Keyword(s):  
Cytochrome P450 ◽  
Radioligand Binding ◽  
Curcuma Longa ◽  
Raw 264.7 Cells ◽  
Cytochrome P450 Enzyme ◽  
Sprague Dawley ◽  
Cytochrome P450 Enzymes ◽  
Boswellia Serrata ◽  
Cell Counts ◽  
Anti Inflammatory

Ayurvedic plants are known for thousands of years to have anti-inflammatory and antiarthritic effect. We have recently shown that BV-9238, a proprietary formulation ofWithania somnifera, Boswellia serrata, Zingiber officinale,andCurcuma longa,inhibits LPS-induced TNF-alpha and nitric oxide production from mouse macrophage and reduces inflammation in different animal models. To evaluate the safety parameters of BV-9238, we conducted a cytotoxicity study in RAW 264.7 cells (0.005–1 mg/mL) by MTT/formazan method, an acute single dose (2–10 g/kg bodyweight) toxicity study and a 180-day chronic study with 1 g and 2 g/kg bodyweight in Sprague Dawley rats. Some sedation, ptosis, and ataxia were observed for first 15–20 min in very high acute doses and hence not used for further chronic studies. At the end of 180 days, gross and histopathology, blood cell counts, liver and renal functions were all at normal levels. Further, a modest attempt was made to assess the effects of BV-9238 (0.5 µg/mL) on six major human cytochrome P450 enzymes and3H radioligand binding assay with human hERG receptors. BV-9238 did not show any significant inhibition of these enzymes at the tested dose. All these suggest that BV-9238 has potential as a safe and well tolerated anti-inflammatory formulation for future use.

Inhibitory Mechanisms of Myricetin on Human and Rat Liver Cytochrome P450 Enzymes

2019 ◽  
Vol 44 (5) ◽  
pp. 611-618 ◽  
Author(s):  
Dan Lou ◽  
Su-su Bao ◽  
Ying-hui Li ◽  
Qian-meng Lin ◽  
Su-fen Yang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Rat Liver ◽  
Cytochrome P450 Enzymes ◽  
Liver Cytochrome ◽  
Inhibitory Mechanisms

A monoclonal antibody to rat liver cytochrome P450 IIC11 strongly and regiospecifically inhibits constitutive benzo[a]pyrene metabolism and DNA binding

1991 ◽  
Vol 4 (4) ◽  
pp. 308-314 ◽  
Author(s):  
Rosa Todorovic ◽  
Prabhaker D. Devanesan ◽  
Ercole L. Cavalieri ◽  
Eleanor G. Rogan ◽  
Sang S. Park ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cytochrome P450 ◽  
Dna Binding ◽  
Rat Liver ◽  
Liver Cytochrome

scholarly journals Characterization of Medicago truncatula (barrel medic) hydroperoxide lyase (CYP74C3), a water-soluble detergent-free cytochrome P450 monomer whose biological activity is defined by monomer–micelle association

2006 ◽  
Vol 395 (3) ◽  
pp. 641-652 ◽  
Author(s):  
Richard K. Hughes ◽  
Eric J. Belfield ◽  
Mylrajan Muthusamay ◽  
Anuja Khan ◽  
Arthur Rowe ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Cytochrome P450 ◽  
Medicago Truncatula ◽  
Water Soluble ◽  
Hydroperoxide Lyase ◽  
Cytochrome P450 Enzyme ◽  
Cytochrome P450 Enzymes ◽  
P450 Enzyme ◽  
Detergent Micelles

We describe the detailed biochemical characterization of CYP74C3 (cytochrome P450 subfamily 74C3), a recombinant plant cytochrome P450 enzyme with HPL (hydroperoxide lyase) activity from Medicago truncatula (barrel medic). Steady-state kinetic parameters, substrate and product specificities, RZ (Reinheitszahl or purity index), molar absorption coefficient, haem content, and new ligands for an HPL are reported. We show on the basis of gel filtration, sedimentation velocity (sedimentation coefficient distribution) and sedimentation equilibrium (molecular mass) analyses that CYP74C3 has low enzyme activity as a detergent-free, water-soluble, monomer. The enzyme activity can be completely restored by re-activation with detergent micelles, but not detergent monomers. Corresponding changes in the spin state equilibrium, and probably co-ordination of the haem iron, are novel for cytochrome P450 enzymes and suggest that detergent micelles have a subtle effect on protein conformation, rather than substrate presentation, which is sufficient to improve substrate binding and catalytic-centre activity by an order of magnitude. The kcat/Km of up to 1.6×108 M−1·s−1 is among the highest recorded, which is remarkable for an enzyme whose reaction mechanism involves the scission of a C–C bond. We carried out both kinetic and biophysical studies to demonstrate that this effect is a result of the formation of a complex between a protein monomer and a single detergent micelle. Association with a detergent micelle rather than oligomeric state represents a new mechanism of activation for membrane-associated cytochrome P450 enzymes. Highly concentrated and monodispersed samples of detergent-free CYP74C3 protein may be well suited for the purposes of crystallization and structural resolution of the first plant cytochrome P450 enzyme.

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