Thalassia testudinum extract modulates hepatic cytochome P450 system in Wistar rats (657.16)

Abstract

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.