The chemical composition and biological properties of Ulva fasciata aqueous-ethanolic extract were examined. Five components were identified in one fraction prepared from the extract by gas chromatography-mass spectrometry, and palmitic acid and its ethyl ester accounted for 76% of the total identified components. Furthermore, we assessed the extract's antioxidant properties by using the DPPH, ABTS, and lipid peroxidation assays and found that the extract had a moderate scavenging effect. In an experiment involving preexposition and coexposition of the extract (1–500 µg/mL) and benzo[a]pyrene (BP), the extract was found to be nontoxic to C9 cells in culture and to inhibit the cytotoxicity induced by BP. As BP is biotransformed by CYP1A and CYP2B subfamilies, we explored the possible interaction of the extract with these enzymes. The extract (25–50 µg/mL) inhibited CYP1A1 activity in rat liver microsomes. Analysis of the inhibition kinetics revealed a mixed-type inhibitory effect on CYP1A1 supersome. The effects of the extract on BP-induced DNA damage and hepatic CYP activity in mice were also investigated. Micronuclei induction by BP and liver CYP1A1/2 activities significantly decreased in animals treated with the extract. The results suggest that Ulva fasciata aqueous-ethanolic extract inhibits BP bioactivation and it may be a potential chemopreventive agent.
Gene regulation involves transcription factors, responsive elements, enhancers, insulators, DNA methylation, histone methylation, acetylation, and deacetylation, among others. In an organism, such components might depend on external factors such as environmental pollution. CYP1A1 gene is inducible by polycyclic aromatic hydrocarbon (PAH) through the aromatic hydrocarbon receptor (AhR). However, exposure to PAHs may affect proteins involved in epigenetic regulation, as well as, CYP1A1 epigenetic regulation. In order to probe this, rat hepatocytes clone‐9 cell line (C9) was exposed to benzo[a]pyrene (BaP), benzofluorene (BF), 2’‐7’‐dimethylbenzantracene (DMBA), 3‐methylcholanthrene (3MC) and DNMTs inhibitor 5’‐Aza‐2’‐deoxycitidine (5AzadC).CYP1A1 gene expression was determined by qPCR and DNMT3a protein level by western blot, showing in both cases an increased with all treatments. However, this effect is exacerbated with a PAH‐AzadC treatment, especially with DMBA. Additionally, treatments also increase DNMT3a protein level in C9 culture. In respect to the positive modulation of CYP1A1 gene expression, we suggest that PAHs do not affect CYP1A1 gene expression only through AhR, but it is also affected by its epigenetic regulation.
We disclose here the effects over several P450 isoforms of one extract from Thalassia testudinum marine plant with cytoprotective and neuroprotective properties. Male Wistar rats were administered orally with 20, 200 and 400 mg/kg of the extract for 10 days. The activities of 7‐ethoxy, 7‐methoxy, 7‐penthoxy and 7‐benzoxyl resorufin‐O‐deethylases, 4‐nitrophenol hydroxylation and erythromycin N‐demethylation were used to asses the function of CYP1A1, CYP1A2, CYP2B1, CYP1B2, 2E1 and 3A in liver microsomes. Protein expressions of cythocromes were determined by western blot and mRNA levels by RT‐PCRq. Microsoms were used as metabolic fraction for the Ames test. Other animals, after receive the same doses of the extract, were administered orally with theophylline (10 mg/kg), blood samples were taken in order to determine the theophylline concentration in plasma. Thalassia testudinum extract (200 mg/kg) was able to induce CYP1A1 (1.5‐fold). Meanwhile, after 400 mg/kg the activity did increase, but no significant differences were found. The lowest dose (20 mg/kg) induced increments of CYP1A2 and 2B1 activities, but no significant differences were seen. A reduction (near to 20%) of CYP2B2, 2E1 and 3A activities was also found. The increase of the CYP1A1 activity was in agreement with the elevation of the protein, but mRNA levels were no modified. The extract increased the mutagenicity of the benzo(a)pyrene at the highest doses (1.8 and 2.3‐fold), confirming its influence on the CYP1A1 activity. Pharmacokinetic profile of theophylline changed in treated rats: Cmax and clearance of theophylline were significantly increased. The elimination rate constant increased twice and the half‐life time was 2‐fold reduced. Thalassia testudinum acts as inducer of the CYP1A1/2 enzymes under these experimentals, suggesting potential herb‐drug interaction when patients use the extract concomitantly or in advance of drugs which are substrates of P450s, especially CYP1A1/2.
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