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

Livan Delgado-Roche; Rebeca Santes-Palacios; José A. Herrera; Sandra L. Hernández; Mario Riera; Miguel D. Fernández; Fernando Mesta; Gabino Garrido; Idania Rodeiro; Javier J. Espinosa-Aguirre

doi:10.20944/preprints202011.0012.v1

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preprints.org > biology and life sciences > biochemistry and molecular biology > doi: 10.20944/preprints202011.0012.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Livan Delgado-Roche

Rebeca Santes-Palacios

^* ,

Javier J. Espinosa-Aguirre

Version 1 : Received: 31 October 2020 / Approved: 2 November 2020 / Online: 2 November 2020 (10:03:37 CET)

A peer-reviewed article of this Preprint also exists.

Delgado-Roche, L.; Santes-Palacios, R.; Herrera, J.A.; Hernández, S.L.; Riera, M.; Fernández, M.D.; Mesta, F.; Garrido, G.; Rodeiro, I.; Espinosa-Aguirre, J.J. Interaction of Thalassia testudinum Metabolites with Cytochrome P450 Enzymes and Its Effects on Benzo(a)pyrene-Induced Mutagenicity. Mar. Drugs 2020, 18, 566. Delgado-Roche, L.; Santes-Palacios, R.; Herrera, J.A.; Hernández, S.L.; Riera, M.; Fernández, M.D.; Mesta, F.; Garrido, G.; Rodeiro, I.; Espinosa-Aguirre, J.J. Interaction of Thalassia testudinum Metabolites with Cytochrome P450 Enzymes and Its Effects on Benzo(a)pyrene-Induced Mutagenicity. Mar. Drugs 2020, 18, 566.

Abstract

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.

Keywords

Thalassia testudinum; thalassiolin B; polyphenols; CYP1A1; benzo[a]pyrene; chemoprevention.

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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