7 results on '"Hernández-Ojeda SL"'
Search Results
2. Piper auritum ethanol extract is a potent antimutagen against food-borne aromatic amines. Mechanisms of action and chemical composition.
- Author
-
Hernández-Ojeda SL, Espinosa-Aguirre JJ, Camacho Carranza R, Amacosta-Castillo J, and Cárdenas-Ávila RI
- Abstract
An ethanol extract of Piper auritum leaves (PAEE) inhibits the mutagenic effect of three food-borne aromatic amines (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx); 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) in the TA98 Salmonella typhimurium strain. Preincubation with MeIQx demonstrated in mutagenesis experiments that inhibition of Cytochrome P450 (CYP), as well as direct interaction between component(s) of the plant extract with mutagens, might account for the antimutagenic observed effect. Gas chromatography/mass spectrometry analysis revealed that safrole (50.7%), α-copaene (7.7%), caryophyllene (7.2%), β-pinene (4.2%), γ-terpinene (4.1%) and pentadecane (4.1%) as the main components of PAEE. Piper extract and safrole were able to inhibit the rat liver microsomal CYP1A1 activity that participates in the amines metabolism, leading to the formation of the ultimate mutagenic/ molecules. According to this, safrole and PAEE inhibited MeIQx mutagenicity but not that of the direct mutagen 2-nitrofluorene. No mutagenicity of plant extract or safrole was detected. This study show that PAEE and its main component safrole are associate with the inhibition of heterocyclic amines activation due in part to the inhibition of CYP1A subfamily activity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.)
- Published
- 2024
- Full Text
- View/download PDF
3. Differential inhibition of naringenin on human and rat cytochrome P450 2E1 activity.
- Author
-
Santes-Palacios R, Olguín-Reyes S, Hernández-Ojeda SL, Camacho-Carranza R, and Espinosa-Aguirre JJ
- Subjects
- Animals, Catalytic Domain, Humans, Molecular Docking Simulation, Rats, Cytochrome P-450 CYP2E1 metabolism, Cytochrome P-450 CYP2E1 Inhibitors pharmacology, Flavanones pharmacology
- Abstract
Cytochrome P450 2E1 (CYP2E1) has been proposed as a molecular target in oxidative stress-associated metabolic diseases. Rats are chosen as model organisms in most experiments studying CYP2E1-related toxicity; however, the human relevance of these results remains unclear. To describe differences in catalysis and inhibition between human and rat CYP2E1, recombinant human and rat CYP2E1 enzymes were treated with different concentrations of naringenin (NAR, 10 nM - 1 mM), and inhibition parameters were calculated. Interspecies differences in the catalytic efficiency for O-demethylation of 7-methoxy-4-(trifluoromethyl)coumarin were revealed (45-fold higher in human CYP2E1 than in the rat enzyme). Additionally, differences in the potency of inhibition of NAR were found (absolute half inhibitory concentration, IC
50 = 204 ± 28 and 69 ± 4 μM; inhibition constant, Ki = 9 ± 2 and 161 ± 20 μM in human and rat CYP2E1, respectively). Although NAR exhibited a noncompetitive mechanism of inhibition of both CYP2E1 enzymes, this compound is an irreversible inhibitor of rat CYP2E1 and a reversible inhibitor of the human enzyme. Molecular docking suggested that differences in the potency of inhibition and time dependence between species could be attributable to the differential interactions of NAR with access channels to the CYP2E1 catalytic site. These results highlight the importance of finding the appropriate model to improve the predictability of animal-based assays for human risk assessment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
4. Neuroinflammation is able to downregulate cytochrome P450 epoxygenases 2J3 and 2C11 in the rat brain.
- Author
-
Navarro-Mabarak C, Loaiza-Zuluaga M, Hernández-Ojeda SL, Camacho-Carranza R, and Espinosa-Aguirre JJ
- Subjects
- Animals, Aryl Hydrocarbon Hydroxylases antagonists & inhibitors, Brain drug effects, Cytochrome P450 Family 2 antagonists & inhibitors, Down-Regulation drug effects, Lipopolysaccharides toxicity, Male, Rats, Rats, Wistar, Steroid 16-alpha-Hydroxylase antagonists & inhibitors, Aryl Hydrocarbon Hydroxylases metabolism, Brain metabolism, Cytochrome P-450 Enzyme System metabolism, Cytochrome P450 Family 2 metabolism, Down-Regulation physiology, Inflammation Mediators metabolism, Steroid 16-alpha-Hydroxylase metabolism
- Abstract
Cytochrome P450 (CYP) epoxygenases have been considered the main producers of epoxyeicosatrienoic acids (EETs) through the oxidation of arachidonic acid (AA). EETs display various biological properties, notably their powerful anti-inflammatory activities. In the brain, EETs have proven to be neuroprotective and to improve neuroinflammation. However, it is known that inflammation could modify CYP expression. We have previously reported that an inflammatory process in astrocytes is able to down-regulate CYP2J3 and CYP2C11 mRNA, protein levels, and activity (Navarro-Mabarak et al., 2019). In this work, we evaluated the effect of neuroinflammation in protein expression of CYP epoxygenases in the brain. Neuroinflammation was induced by the intraperitoneal administration of LPS (1 mg/kg) to male Wistar rats and was corroborated by IL-6, GFAP, and Iba-1 protein levels in the cortex over time. CYP2J3 and CYP2C11 protein levels were also evaluated in the cortex after 6, 12, 24, 48, and 72 h of LPS treatment. Our results show for the first time that neuroinflammation is able to downregulate CYP2J3 and CYP2C11 protein expression in the brain cortex., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
5. Reduction in CYP1A1 and 2B2 activity at low oxygen tension.
- Author
-
Hernández-Gutiérrez L, Camacho-Carranza R, Hernández-Ojeda SL, Govezensky T, Olguín-Reyes SR, and Espinosa-Aguirre JJ
- Abstract
The Cytochrome P450 (CYP) enzyme family comprises a wide array of monooxygenases involved in the oxidation of endobiotic and xenobiotic molecules. The active site of a CYP enzyme contains an iron protoporphyrin center coordinated to a cysteine thiolate, and then, molecular oxygen is associated with the iron to be converted into dioxygen complex plus substrate. Reduction by CYP reductase expedites hydroxylation of the compound. In this oxidation reaction, insufficient oxygen molecules would affect enzyme catalysis. Nevertheless, biochemical data about CYP kinetics at low oxygen concentrations are not available. In this work, we present the results on the variation in rat liver microsomal CYP Vmax app and Km app under normal and hypoxic conditions. Using alkoxyresorufin molecules as substrates, the Vmax/Km ratios for resorufin production decreased from 426 to 393 for CYP1A1 and from 343 to 202 for CYP2B1 at a low oxygen concentration (4.1 ppm) compared to the ratios observed at a normal oxygen concentration (6.5 ppm). Additionally, the bacterial mutagenicity of 2-aminoanthracene and cyclophosphamide, decreased by 32% and 42%, respectively, at low oxygen concentrations. These results support the hypothesis that low oxygen availability is implicated in the low efficiency of substrate oxidation by CYP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
6. Human CYP1A1 inhibition by flavonoids.
- Author
-
Santes-Palacios R, Marroquín-Pérez AL, Hernández-Ojeda SL, Camacho-Carranza R, Govezensky T, and Espinosa-Aguirre JJ
- Subjects
- Amino Acids metabolism, Antimutagenic Agents pharmacology, Computer Simulation, Flavones chemistry, Flavones pharmacology, Humans, Models, Molecular, Molecular Docking Simulation, Mutagenicity Tests, Mutagens pharmacology, Recombinant Proteins, Structure-Activity Relationship, Antineoplastic Agents, Phytogenic pharmacology, Cytochrome P-450 CYP1A1 antagonists & inhibitors, Flavonoids pharmacology
- Abstract
Cytochrome P4501A1 (CYP1A1) is involved in the metabolism of several genotoxic/carcinogenic environmental xenobiotics including polycyclic aromatic hydrocarbons (PAHs) like benzo[a]pyrene. Several authors had proposed CYP1A inhibition as a plausible strategy for cancer chemoprevention. Using ethoxyresorufin O-deethylase activity (EROD), we tested the inhibitory properties of nine flavonoids: quercetin, miricetin, luteolin, fisetin, morin, kaempferol, 5-hydroxyflavone (5-HF), 3-hydroxyflavone (3-HF), and flavone (F) against human recombinant CYP1A1. The last three compounds exerted the highest inhibitory effect with IC
50 values of 0.07, 0.10 and 0.08 μM respectively; the more hydroxyl-groups were present, the lower the potency of inhibition was. Biochemical characterization leads to the conclusion that flavone and its hydroxy derivatives are mixed-type inhibitors. In silico studies have shown that, Phe224 and other aromatic residues in the human CYP1A1 active site play an important role in flavonoid-CYP interaction, through a π/π stacking between the aminoacid and the flavonoid C-ring. Outside the active site, the three flavonoids bind preferentially between A and K helices of the enzyme. Results from the Ames test using human S9 fraction revealed that none of the three compounds was mutagenic. We can consider 5-HF, 3-HF, and F as potential chemopreventive agents against genotoxic damage caused by metabolites resulting from CYP1A1 activity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
7. Effect of [Cu(4,7-dimethyl-1,10-phenanthroline)(acetylacetonato)]NO3, Casiopeína III-Ea, on the activity of cytochrome P450.
- Author
-
Campero-Peredo C, Bravo-Gómez ME, Hernández-Ojeda SL, Olguin-Reyes Sdel R, Espinosa-Aguirre JJ, and Ruiz-Azuara L
- Subjects
- Animals, Kinetics, Male, Microsomes, Liver drug effects, Microsomes, Liver metabolism, Rats, Wistar, Antineoplastic Agents pharmacology, Coordination Complexes pharmacology, Cytochrome P-450 Enzyme Inhibitors pharmacology, Cytochrome P-450 Enzyme System metabolism, Phenanthrolines pharmacology
- Abstract
Casiopeína III-Ea (Cas III-Ea(1)) is a copper complex with antiproliferative and antitumor activities, designed to act via alternative mechanisms of action different from Cisplatin. This compound has also been well characterized in preclinical test and pharmacokinetic analysis, being a good candidate for clinical phases. Since very little is known about the processes of biotransformation of therapeutic metal based drugs, this paper report the first approach to the study of the interaction between metal complex Cas III-Ea and cytochromes P450 with the aim to find out possible biotransformation pathways for this complexes and feasible drug-drug interactions. Results showed that Cas III-Ea is a strong irreversible competitive inhibitor of CYP1A1 (IC50 = 7.5 ± 1.0 μM; Ki = 240 nM). The magnitude of values indicate that it is necessary to be taken into account such effect when analyzing possible drug interactions with these new drugs in order to prevent adverse reactions derived from this inhibition., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.