Prolonged Fructose Feeding and Aldose Reductase Inhibition: Effect on the Polyol Pathway in Kidneys of Normal Rats

Abstract

The effects of diets with differing carbohydrate composition on the kidney polyol pathway were investigated. The diets employed were F = fructose rich, G = glucose rich, S = cornstarch rich, and were fed for 30 days to six groups of 12 normal male Sprague-Dawley rats with and without addition of the aldose reductase inhibitor tolrestat (T). Fructose feeding resulted in higher kidney sorbitol levels (F = 0.847 ± 0.152, G = 0.354 ± 0.087, S = 0.207 ± 0.041 μM/g wet wt, P < 0.05). This was not observed in the tolrestat-treated animals (F + T = 0.182 ± 0.024, G + T = 0.149 ± 0.021, S + T = 0.152 ± 0.020 μM/g wet wt). Aldose reductase activity was reduced with tolrestat administration (F = 0.0208 ± 0.0023, F + T = 0.0048 ± 0.0005; G = 0.0210 ± 0.0002, G + T = 0.0059 ± 0.0008; S = 0.0227 ± 0.0022, S + T = 0.0062 ± 0.0007 μU). Myoinositol levels did not differ among groups (F = 1.973 ± 0.182, G = 2.291 ±0.307, S = 2.066 ± 0.155 μM/g wet wt), but tended to increase with aldose reductase inhibition (F + T = 2.253 ± 0.186, G + T = 2.713 ± 0.166, S + T = 2.618 ± 0.221 μM/g wet wt). Plasma glucose was higher in the fructose-fed rats (F = 10.78 ± 0.55, G = 9.09 ± 0.058, S = 9.03 ± 0.52, F + T = 9.75 ± 0.61, G + T = 8.42 ± 0.64, S + T = 8.81 ± 0.49 mM/liter). It is concluded that prolonged fructose feeding results in the accumulation of sorbitol in the kidney, caused by increased flux of glucose through the polyol pathway. This can be prevented by aldose reductase inhibition.