We previously reported a practical procedure for evaluating the hyperuricemic effects of drugs by using rats treated with a urate oxidase inhibitor, potassium oxonate. Fructose and xylitol, which have hyperuricemic effects widely documented in clinical use, were useful model compounds for this assay method. However, the mechanisms by which the hyperuricemic effects were induced in the animals were not always the same. Fructose rapidly but transiently increased plasma uric acid in rats treated with potassium oxonate, while xylitol gradually increased it from at least two hours later. The increase of plasma uric acid caused by fructose followed an appreciable reduction of the hepatic ATP level, but xylitol caused no change in the hepatic adenine nucleotides during the duration of the hyperuricemic effect. Infusion of a high concentration of fructose solution for 15 min from the portal vein induced a more obvious decrease of the hepatic ATP level together with an apparent increase of plasma uric acid in arterial blood. Xylitol caused no such effects. Moreover, fructose obviously increased uric acid production in perfused rat liver by a cross-circulation technique with blood donor animals, but xylitol again had no effect. Both fructose and xylitol showed no appreciable effects on plasma and urinary uric acid levels in rats, in which the plasma uric acid level was maintained by treatments with allopurinol, potassium oxonate and exogenously administered uric acid. Accordingly, we concluded that both sugars showed hyperuricemic effects due to stimulation of uric acid production, but the mechanisms were obviously different. The hyperuricemic effect of fructose must be due to a rapid degradation of hepatic ATP as well documented by earlier workers, but that of xylitol may depend upon the stimulation of purine biosynthesis de novo.
Hyperuricemia was noted in 22.4% of 20,723 consecutive serum urate measurements at our hospital and hypouricemia was noted in 1.8%. The purpose of the present study was to determine the clinical significance of these abnormal serum urate values. The results are as follows: 1. In hyperuricemia, the frequency of the cardio-vascular diseases was 55.6%. The frequency of malignant tumor, urolithiasis, renal failure, liver dysfunction and hypercholesteremia was higher than that of normal controls significantly. In addition, it was found in hyperuricemia to correlate between the degree of serum urate concentration and the frequency of gouty arthritis, ishemic heart disease, cerebral vascular disturbance and renal failure. 2. In hypouricemia, malignant tumor, low proteinemia, liver dysfunction and diabetes mellitus were commonly complicated. The pathogenesis of liver dysfunction and diabetes showing hypouricemia is an attractive study in comparison to that with hyperuricemia 3. Hypouricemia is significant in so-called idiopathic hypouricemia but less in clinical occurrence.
The pharmacological studies of CG-120 (Uralyt-U) were investigated in rats and rabbits. CG-120 indicated a marked alkalogenic effects against normal rats, but its effects were weak in rabbits. CG-120 also showed protective and curative effects on acidotic rats induced by 0.5% anmmonium chloride. On serum electrolytes in rats CG-120 were no influence, but sodium bicarbonate were the breakdown of electrolyte balance on rat serum. In addition, CG-120 stimulated urinary excretion of uric acid with increasing of urinary volume in rats treated by 3% oxonic acid and 1% uric acid. These observations suggested that CG-120 may be useful agents for the therapy of hyperuricemias (gout, urinary caluclus, etc.) as basic alkalogenic-drug.
A 14-year-old boy with Lesch-Nyhan syndrome was treated for hyperuricemia by allopurinol.3 years later he developped many stones and the stone analysis revealed xanthine. Iatrogenic xanthine stone formation by allopurinol are reported in Lesch-Nyhan syndrome and in patients with progressive cancer. Etiology and prevention of xanthine stone formation is briefly discussed.