Interaction of Thalassia testudinum Metabolites with Cytochrome P450 Enzymes and Its Effects on Benzo(a)pyrene-Induced Mutagenicity

The aim of the present work was to evaluate the effects of Thalassia testudinum hydroethanolic extract, its polyphenolic fraction, and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by Ames test. Finally, the antimutagenic effect of Thalassia testudinum (100 mg/kg) was assessed in a BP-induced mutagenesis in mice. The tested products significantly (p<0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16±9.09 μg/mL, 5.96±1.55 μg/mL and 3.05±0.89 μg/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1±63.40 μg/mL and 203.10±17.29 μg/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit (p<0.05) benzo[a]pyrene (BP)-induced mutagenicity in vitro. Furthermore, oral doses of Thalassia testudinum (100 mg/kg) significantly reduced (p<0.05) the BP-induced micronuclei and oxidative damage, together with an increase of glutathione, in mice. In summary, Thalassia testudinum metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation. Thus, the metabolites of T. testudinum may represent a potential source of chemopreventive compounds for adjuvant therapy of cancer.

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Interaction of Thalassia testudinum Metabolites with Cytochrome P450 Enzymes and Its Effects on Benzo(a)pyrene-Induced Mutagenicity

Marine Drugs ◽

10.3390/md18110566 ◽

2020 ◽

Vol 18 (11) ◽

pp. 566 ◽

Cited By ~ 1

Author(s):

Livan Delgado-Roche ◽

Rebeca Santes-Palacios ◽

José A. Herrera ◽

Sandra L. Hernández ◽

Mario Riera ◽

...

Keyword(s):

Thalassia Testudinum ◽

Cytochrome P450 Enzymes ◽

Metabolizing Enzymes ◽

Antimutagenic Effect ◽

Potential Source ◽

Mutagenicity Assay ◽

Induced Mutagenesis ◽

Oral Doses ◽

Hydroethanolic Extract

The aim of the present work was to evaluate the effects of Thalassia testudinum hydroethanolic extract, its polyphenolic fraction and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by an Ames test. Finally, the antimutagenic effect of Thalassia testudinum (100 mg/kg) was assessed in BP-induced mutagenesis in mice. The tested products significantly (p < 0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16 ± 9.09 μg/mL, 5.96 ± 1.55 μg/mL and 3.05 ± 0.89 μg/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1 ± 63.40 μg/mL and 203.10 ± 17.29 μg/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit (p < 0.05) BP-induced mutagenicity in vitro. Furthermore, oral doses of Thalassia testudinum (100 mg/kg) significantly reduced (p < 0.05) the BP-induced micronuclei and oxidative damage, together with an increase of reduced glutathione, in mice. In summary, Thalassia testudinum metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation, arresting the oxidative and mutagenic damage. Thus, the metabolites of T. testudinum may represent a potential source of chemopreventive compounds for the adjuvant therapy of cancer.

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Antimutagenic effect of lectin and N-methyl-N’-nitro-N-nitrosoguanidine on induced mutagenesis in mammalian cells in vitro

Cytology and Genetics ◽

10.3103/s0095452707060096 ◽

2007 ◽

Vol 41 (6) ◽

pp. 381-384 ◽

Cited By ~ 1

Author(s):

O. O. Kovalenko ◽

L. L. Lukash

Keyword(s):

Mammalian Cells ◽

Antimutagenic Effect ◽

Induced Mutagenesis

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STEROID HORMONE METABOLISM IN RESPONSIVE TISSUES IN VITRO

Acta Endocrinologica ◽

10.1530/acta.0.068s279 ◽

1971 ◽

Vol 68 (1_Suppl) ◽

pp. S279-S294 ◽

Cited By ~ 12

Author(s):

Paul Robel

Keyword(s):

Steroid Hormone ◽

Physiological Activity ◽

Physiological State ◽

Target Cells ◽

Target Tissue ◽

Hormone Metabolism ◽

Metabolizing Enzymes ◽

Relationship Of

ABSTRACT Of the information available on steroid hormone metabolism in responsive tissues, only that relating hormone metabolism to physiological activity is reviewed, i. e. metabolite activity in isolated in vitro systems, binding of metabolites to target tissue receptors, specific steroid hormone metabolizing enzymes and relationship of hormone metabolism to target organ physiological state. Further, evidence is presented in the androgen field, demonstrating 5α-reduced metabolites, formed inside the target cells, as active compounds. This has led to a consideration of testosterone as a »prehormone«. The possibility that similar events take place in tissues responding to progesterone is discussed. Finally, the role of hormone metabolism in the regulation of hormone availability and/or renewal in target cells is discussed. In this context, reference is made to the potential role of plasma binding proteins and cytosol receptors.

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Effects of Magnolol, a Biphenolic Component of Magnolia obovata T, on Human Cytochrome P450 Enzymes in vitro

The Korean Tea Society ◽

10.29225/jkts.2017.23.1.37 ◽

2017 ◽

Vol 23 (1) ◽

pp. 37-44

Author(s):

Jin Kim

Keyword(s):

Cytochrome P450 ◽

Cytochrome P450 Enzymes ◽

Magnolia Obovata ◽

Human Cytochrome

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In vitro inhibitory mechanisms and molecular docking of 1′-S-1′-acetoxychavicol acetate on human cytochrome P450 enzymes

Phytomedicine ◽

10.1016/j.phymed.2017.05.002 ◽

2017 ◽

Vol 31 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

A.K.M. Mahmudul Haque ◽

Kok Hoong Leong ◽

Yoke Lin Lo ◽

Khalijah Awang ◽

Noor Hasima Nagoor

Keyword(s):

Cytochrome P450 ◽

Molecular Docking ◽

Cytochrome P450 Enzymes ◽

Inhibitory Mechanisms ◽

Human Cytochrome

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The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo

Pharmaceutics ◽

10.3390/pharmaceutics13020186 ◽

2021 ◽

Vol 13 (2) ◽

pp. 186

Author(s):

Maria Natalia Calienni ◽

Daniela Maza Vega ◽

C. Facundo Temprana ◽

María Cecilia Izquierdo ◽

David E. Ybarra ◽

...

Keyword(s):

Side Effects ◽

Water Solubility ◽

Polymeric Micelles ◽

Skin Penetration ◽

Distribution Volume ◽

And Performance ◽

Oral Doses ◽

Advanced Basal Cell Carcinoma

Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems were the most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformable liposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can be loaded in several delivery systems for topical application. These findings may be also useful for the consideration of topical delivery of other drugs with a low water solubility.

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In vitro study on the effect of cornin on the activity of cytochrome P450 enzymes

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03309-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qun Zhang ◽

Zengqiang Qu ◽

Yanqing Zhou ◽

Jin Zhou ◽

Junwei Yang ◽

...

Keyword(s):

Cytochrome P450 ◽

Drug Interaction ◽

Liver Microsomes ◽

In Vitro Study ◽

Inhibitory Effect ◽

Dependent Manner ◽

Cytochrome P450 Enzymes ◽

Drug Drug Interaction ◽

Dose Dependent

Abstract Background Cornin is a commonly used herb in cardiology for its cardioprotective effect. The effect of herbs on the activity of cytochrome P450 enzymes (CYP450s) can induce adverse drug-drug interaction even treatment failure. Therefore, it is necessary to investigate the effect of cornin on the activity of CYP450s, which can provide more guidance for the clinical application of cornin. Methods Cornin (100 μM) was incubated with eight isoforms of CYP450s, including CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6, and 2E1, in pooled human liver microsomes. The inhibition model and corresponding parameters were also investigated. Results Cornin exerted significant inhibitory effect on the activity of CYP3A4, 2C9, and 2E1 in a dose-dependent manner with the IC50 values of 9.20, 22.91, and 14.28 μM, respectively (p < 0.05). Cornin inhibited the activity of CYP3A4 non-competitively with the Ki value of 4.69 μM, while the inhibition of CYP2C9 and 2E1 by cornin was competitive with the Ki value of 11.31 and 6.54 μM, respectively. Additionally, the inhibition of CYP3A4 by cornin was found to be time-dependent with the KI/Kinact value of 6.40/0.055 min− 1·μM− 1. Conclusions The inhibitory effect of cornin on the activity of CYP3A4, 2C9, and 2E1 indicated the potential drug-drug interaction between cornin and drugs metabolized by these CYP450s, which needs further investigation and validation.

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