THESIS: J.C. Freitas submitted this thesis to obtain the degree of Associate Professor in Physiology, publicly examined at the Biosciences Institute of the University of São Paulo, São Paulo, Brazil, in 1988.
ABSTRACT. An increasing number of new bioactive organic compounds from marine organisms are reported in the literature, particularly from algae and invertebrates. The experimental approach consists of a systematic investigation about the action of crude or purified extracts on physiological preparations or whole animals to outline the profile of their biological activity and mechanism of action. In the present work, methanol extracts from species of seaweeds collected on the State of São Paulo coast produced different pharmacological effects. In toad's heart they showed positive inotropy and chronotropy (Bryopsis pennata-1), negative inotropy and chronotropy (Arthrocardia gardneri-2, Jania rubens-3, Galaxaura frutescens-4 and Levringia brasiliensis-5); in toad's sciatic nerve, inhibition of compound action potentials (2,3,4 and 1) and in mouse's phrenic nerve-hemidiaphragm, depression of the muscular twich induced by electric stimulation (2,3,4 and 5). Using liquid chromatografic fluorometric analysis of A. gardneri purified extract, gonyautoxins I, IV (saxitoxin analogues) and tetrodotoxin were found. In a mussel sample (Perna perna) neosaxitoxin and gonyautoxins I, IV and III were detected. Mussels are related to paralytic shellfish poisoning in many regions of the world, accumulating toxins from bacteria and dinoflagellates. These toxins depress cellular excitability by blocking Na+ channels. The dinoflagellate Alexandrium fraterculus, reported to be non-toxic in Japanese waters, was found on the State of São Paulo coast, but no one knows whether they contain neurotoxins or not. As far as we know, Japanese authors have reported that bacteria strains associated with dinoflagellates are their source of neurotoxins. Algae extracts were studied on fertilized sea-urchin egg development showing inhibition of cleavage, abnormal cleavages and other anomalies. In other experiments, using pure compounds an inhibition of platelet aggregation by an antiinflammatory sesterterpenoid isolated from the Pacific Ocean sponge Luffariella variabillis was found. This compound named manoalide, seems to be a useful drug in the treatment of diseases due to its intense inhibition of platelet aggregation. Another pure compound studied was caissarone, an iminopurine isolated from the sea anemone Bunodosoma caisarum that increase motility in isolated mammalian gut preparations. In guinea-pig longitudinal muscle/myenteric plexus preparation, caissarone increases the response elicited by transmural electric stimulation in a dose-dependent manner and in a concentration as low as 2.8 µg/ml bath. In extracellular recordings using suction electrodes attached to the guinea-pig gut preparation, caissarone induces a frequency increase of action potential discharges and this effect was blocked by procaine and tetrodotoxin. The possible mechanism of action could be an antagonism of purinergic transmitters acting on the gut wall involved in the tonic inhibition of intestinal motility. Further studies on these subjects are necessary, but the findings reported here are important in terms of future envenoming outbreaks on the Brazilian coast.
REFERENCES
01 FREITAS JC., RODRIGUE F., LAVAUD P., MENCIA-HUERTA JM., BRAQUET P. Inhibition of platelet aggregation by manoalide. Preliminary results. Braz. J. Med. Biol. Res., 1988, 21, 337-40.
02 FREITAS JC. Biomedical importance of marine natural products.Ciencia & Cultura, 1990, 42, 20-4.
03 FREITAS JC., SAWAYA MI. Increase of mammalian intestinal motility by the marine natural product, caissarone.Toxicon, 1990, 28, 1029-37.
CORRESPONDENCE TO:
J.C. FREITAS - Departamento de Fisiologia - Instituto de Biociências da Universidade de São Paulo, Rua do Matão, Travessa 14, No. 101. CEP 05508-900, São Paulo, SP, Brasil.
Publication Dates
-
Publication in this collection
08 Jan 1999 -
Date of issue
1995
