STUDY OF THE INTERACTION OF AN EXTRACT OBTAINED FROM THE MARINE PLANT Thalassia testudinum WITH PHASE I METABOLISM IN RATS

Resumen

The effects of an extract from the marine plant Thalassia testudinum on rat liver cytochrome P450s were investigated. Male Wistar rats were administered for 10 days with 20, 200 or 400 mg/kg oral doses of the extract. The activities of CYP1A1/A2, CYP2B1/B2, CYP2E1 and CYP3A were evaluated. CYP1A1 activity and protein content increased after 200 mg/kg of the extract but mRNA levels remain unchanged. The activity of other CYP isoforms did not change. The S9 fraction derived from the livers of the rats treated with the extract was used to evaluate the effects of this product on the mutagenic activation of benzo[a]pyrene. The number of Salmonella mutant colonies induced by benzo[a]pyrene in the presence of S9 obtained from animals treated with 200 and 400 mg/kg of the extract were respectively 1.8 and 2.3-fold higher than controls, while it was reduced at the 20 mg/kg dose. This strongly support the idea that the extract modulated the liver enzymes which transform benzo[a]pyrene into mutagenic metabolites. Another set of male rats were treated for 10 days with the same doses. Sixteen hours later, rats received oral doses of theophylline (10 mg/kg), blood samples were extracted from each animal at 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 h after administration and plasma theophylline concentration was measured. Pre-treatment with the extract increased theophylline clearance. Our results suggested that the extract modify CYP1A in vivo activity and metabolism-based pharmacokinetic interactions between the extract and CYP1A substrates may occur in vivo.