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SECOND INTERNATIONAL SYMPOSIUM
ON THE ROLE OF SOY
IN PREVENTING AND TREATING CHRONIC DISEASE

September 15-18, 1996
Brussells, Belgium

SCIENTIFIC PROGRAM
(Oral Abstracts)

Soy and Kidney Function

Soy Isoflavonoids Possess Biological Activities of Loop-Diuretics.
Martinez, R.M.; Gimenez, I.; Lou, M.; Mayoral, J.A.*; Alda, O.J.
Department of Pharmacology and Physiology, Faculty of Medicine and *Department of Organic Chemistry, Faculty of Sciences, Zaragoza (SPAIN).

Introduction
Previous results (see abstract nr. 14) showed that equol and genistein have a similar ion transport inhibitory pattern to that of furosemide, a potent diuretic and smooth muscle vasorelaxant. The aim of the present study is to investigate isoflavonoids effects on kidney tubular and hemodynamic parameters and to compare them with the effects of an equivalent dose of furosemide (in terms of cotransport inhibition).
Methods
Kidneys from male Wistar rats were isolated and perfused according to previously detailed techniques (Maack, Am. J. Physiol, 238: F71-F78, 1980). After twenty minutes for equilibration 2 mg furosemide (from SIGMA), 5 mg equol (synthesized by one of us: J.A.M.) or genistein (from SIGMA) dissolved in 60 L DMSO, or vehicle alone, were added to the perfusate. Each clearance period lasted for 10 minutes; perfusate samples were taken in the midpoint of each period. Urine was measured gravimetrically, electrolytes by flame photometry and creatinine using a colorimetric kit. Perfusion pressure and renal perfusion flow were recorded by means of a mercury manometer and a Brooks flowmeter, respectively. Results are expressed as the mean+/-standard error of mean of at least four different experiments.

Results
1. Effects on tubular parameters.
Table 1 shows proportional increments, respect to vehicle kidneys, in diuresis (DV), natriuresis (DUNaV) and kaliuresis (DUKV) at 30 min after the addition of the drug:

Drug DV DUNaV DUKV

Furosemide 2 mg 2.97+/-0.1 6.57+/-0.6 3.78+/-0.2
Genistein 3.19+/-0.3 6.45+/-0.3 3.65+/-0.2
Equol 2.71+/-0.2 4.29+/-0.1 2.92+/-0.4

2. Change of hemodynamic values
Table 2 shows proportional variations, respect to vehicle kidneys, in glomerular filtration rate GFR), filtration fraction ( FF) and renal vascular resistance ( RVR) at 30 min after the addition of the drug:

Drug DGFR DFF DRVR

Furosemide 2 mg 1.21+/-0.2 1.25+/-0.3 0.90+/-0.04
Genistein 5 mg 1.14+/-0.3 1.18+/-0.1 0.82+/-0.02
Equol 5 mg 1.20+/-0.3 1.22+/-0.2 0.94+/-0.08

Conclusions
Both genistein and equol stimulated fluid and electrolyte excretion by the rat isolated perfused kidney. Their stimulatory pattern was similar to that observed with furosemide. Surprisingly, genistein was more potent than equol.

All three drugs increase GFR and FF in the same extent. Furosemide and equol did not elicite significant hemodynamic changes, possibly because we did not preconstrict the kidneys. However, genistein was able to vasodilate the isolated kidney.
Isoflavonoids are being attributed with beneficial properties in many disease states, like heart and kidney disease. In such cases, loop diuretics have proven themselves to be

beneficial; our results establish several similiarities between loop diuretics and soy isoflavonoids. To what extent the usefulness of soy isoflavonoids in kidney or heart disease could derive of such similarities remain unexplored.

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