Aim: 

The soy phytoestrogen genistein exerts numerous beneficial effects in the organism but its mechanism of action is not well understood. Recently genistein was demonstrated to affect different ion transport mechanisms in various cell types. In this study we tested the soy isoflavonoid in the intestine of a marine teleost, an absorptive epithelium similar in its transport properties to the thick ascending limb of Henle's loop in mammalian kidney.

Methods: 

Sea water adapted eels were used. The isolated intestine was mounted in a modified Ussing chamber and electrophysiological techniques were employed.

Results: 

We found that the addition of 10^-4 M genistein in either the serosal or the mucosal bath reversibly reduced the short circuit current (I_sc), due to net Cl^- absorption in the control conditions. It did not alter tissue conductance, thus excluding an effect on the paracellular pathway. Genistein and various loop diuretics (bumetanide, furosemide, piretanide, torasemide) were tested in dose-response experiments. The results obtained showed that the effect of genistein on I_sc was comparable to that produced by the diuretics. The maximum reduction was observed with 10^-4 M genistein. In addition the effect of the isoflavonoid was negligible when tested after luminal bumetanide (10^-5 M) or furosemide (10^-4 M) had produced their maximal inhibition of I_sc . On the contrary genistein produced its usual effect in tissues preincubated with either luminal glibenclamide (10^-4 M) or NPPB (10^-4 M), two CFTR inhibitors.

Conclusions: 

Our research suggests that genistein exhibits biological activity of loop diuretic as demonstrated in rat kidney, while it seems to exclude the activation of CFTR by genistein observed in human airway epithelial cells and in rat aorta. Cotransport inhibition by genistein may be related to its ability for inhibiting tyrosine kinase activity.