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

• Published in: Marine drugs 2020-11, Vol.18 (11), p.566
• Main Authors: Delgado-Roche, Livan, Santes-Palacios, Rebeca, Herrera, José A, Hernández, Sandra L, Riera, Mario, Fernández, Miguel D, Mesta, Fernando, Garrido, Gabino, Rodeiro, Idania, Espinosa-Aguirre, Jesús Javier
• Format: Article
• Language: English
• Subjects: Activation, Metabolic; Air pollution; Ames test; Animals; Antimutagenic Agents - isolation & purification; Antimutagenic Agents - pharmacology; Antioxidants; Aromatic hydrocarbons; Benzo(a)pyrene; Benzo(a)pyrene - metabolism; Benzo(a)pyrene - toxicity; Biotransformation; Carcinogens; chemoprevention; CYP1A protein; CYP1A1; Cytochrome; Cytochrome P-450 CYP1A1 - antagonists & inhibitors; Cytochrome P-450 CYP1A1 - metabolism; Cytochrome P-450 CYP1A2 - metabolism; Cytochrome P-450 CYP1A2 Inhibitors - isolation & purification; Cytochrome P-450 CYP1A2 Inhibitors - pharmacology; Cytochrome P-450 Enzyme Inhibitors - isolation & purification; Cytochrome P-450 Enzyme Inhibitors - pharmacology; Cytochrome P450; Cytochromes; Cytochromes P450; Damage; Deoxyribonucleic acid; DNA; DNA Damage - drug effects; Enzymes; Evaluation; Flavonoids; Flavonoids - isolation & purification; Flavonoids - pharmacology; Glutathione; Humans; Hydrocharitaceae - metabolism; Isoenzymes; Kinetics; Lung cancer; Metabolism; Metabolites; Micronuclei; Micronuclei, Chromosome-Defective - chemically induced; Micronucleus Tests; Mutagenesis; Mutagenicity; Natural products; Oxidative Stress - drug effects; Pollutants; Polyphenols; Polyphenols - isolation & purification; Polyphenols - pharmacology; Pyrene; Rats; Salmonella typhi - drug effects; Salmonella typhi - genetics; Thalassia testudinum; thalassiolin B
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md18110566

The aim of the present work was to evaluate the effects of 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 (100 mg/kg) was assessed in BP-induced mutagenesis in mice. The tested products significantly ( < 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 ( < 0.05) BP-induced mutagenicity in vitro. Furthermore, oral doses of (100 mg/kg) significantly reduced ( < 0.05) the BP-induced micronuclei and oxidative damage, together with an increase of reduced glutathione, in mice. In summary, 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 may represent a potential source of chemopreventive compounds for the adjuvant therapy of cancer.