Efeito da microcistina-LR em rim e intestino isolados e na secreção de insulina

Abstract

Microcystin -LR is a toxin produced by ffeshwater cyanobacteria wildly spread in water reservoirs, representing a health risk to animais and humans. In th is work it was investigated the effects of mycrocystin-LR (MCLR) in the isolated aorta rings using the doses of 1,3, 10, 30, 100 and 300 ng/mL; the renal effects of the supernatant from macrophages stimulated by this toxin (1 pg/mL); intestlne water and electrolytes secretion induced by MCLR (1 pg/rnL) and by the supernatant of activated macrophages in isolated loop and isoiated perfused intestine; the antimitotic and theratogenic activity of MCLR in sea. urchin Lytechinus variegates eggs; as well as insulin secretion using isoiated Langerhans islets. It was observed that microcystin-LR did not cause any alteration in the isolated aorta rings method. On the other hand, the supernatant of MCLR activated macrophages altered significantly (*p<0,05) the renal perfusion pressure, renal vascular resistance, urinary flow, glomerular filtration rate, the percentage of sodium tubular transport and the percentage of proximal sodium and potassium tubular transport afiter using the isolated perfused rat kidney method. Cycloheximide (10'5 M), dexamethasone (10‘5 M) and quinacrine (1O'? M) blocked almost all renal alterations promoted by microcystin, while thalidomide (1.5 x 10'5 M) reverted only the effects in renal vascular resistance. These results suggest that microcystin-LR induced activated macrophages to liberate some mediators, which promoted in vitro nephrotoxicity. It was aiso demonstrated that microcystin-LR and the supernatant of macrophages stimulated by this toxin induced water and electrolytes (sodium, potassium and chloride) intestine secretion in a similar pattern to cholera toxin, using isolated loop and intestine perfusion. Microcystin-LR did not altered the embryonic growing rate of the sea urchin Lythechinus variegates eggs and larva! stage, however, it was able to increase glucose induced insulin secretion associated to pancreatic p cells apoptosis. fherefore, these data suggest that macrophages, stimulated by microcystin-LR, induced protein mediator release, which were able to cause nephrotoxicity and intestine secretion. In addition, this toxin was capable to cause insulin secretion of pancreatic cells, probably by the increase of calcium influx.