benzofurans and Kidney-Calculi

The aim of this study was to investigate the role of oxidative stress in cystine crystal formation and whether salvianolic acid B, a natural antioxidant, could prevent cystine-mediated oxidative injury in vivo and in vitro. The levels of oxidative stress and antioxidase activity in cystine stone patients were assessed. Then, the oxidative stress exerted by cystine on human kidney-2 (HK-2) cell viability and biochemical parameters including antioxidase activity and antioxidant protein expression were evaluated, and the protective action of salvianolic acid B was also examined. Finally, salvianolic acid B was tested to determine whether it could prevent or reduce renal crystal formation in Slc7a9 knockout mice. The activity levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were decreased, and the amount of malondialdehyde (MDA) was increased in patients with cystine stones compared with people without cystine stones (p < 0.05). Significant reductions in cell viability, antioxidase activity and antioxidant protein expression levels were found in the cystine group compared with controls. However, such oxidative injuries were prevented by salvianolic acid B. In the animal study, loose crystals with white spots were seen in the renal parenchyma, bilateral renal pelvis and bladders in the Slc7a9 knockout group. In contrast, no renal crystals were seen in the control group, and markedly fewer crystals with significantly higher antioxidase activity and diminished oxidative stress were detected in the salvianolic acid B group. Cystine cytotoxicity in vitro and cystine stone formation in vivo were associated with oxidative stress, and salvianolic acid B could protect against cystine stone-induced injury.

Topics: Animals; Benzofurans; Cells, Cultured; Cystine; Humans; Kidney Calculi; Male; Mice; Mice, Knockout; Oxidative Stress

In 13 patients suffering from recurrent calcium-oxalate urolithiasis the circadian course in the excretion of urinary components was investigated before and during treatment with a combination of allopurinol and benzbromarone. The patients were given a diet standardized in food and liquid intake. Urine was collected for 3 days every 3 h from the 7th day of standard diet. On days 8 and 9 each patient received one tablet of the combination. On all 3 days of urine collection a constant circadian course of urine volume was observed; pH values also showed a nearly identical course on all 3 days with increased daytime and low night values. Maximum excretion of uric acid under dietary conditions was discovered between 11 a.m. and 5 p.m. (day 7). After the first application of the compound (day 8, 8 a.m.) a transient increase in uric acid excretion was observed in the third collection period (2-5 p.m.), followed by a sharp decrease. Following the second application (day 9) the transient increase of the uric acid excretion was clearly diminished. Uric acid excretion in the 24-h urine also decreased steadily from 3.46 mmol/day (control) to 3.25 and 3.06 mmol/day (treatment). Serum uric acid decreased significantly from 324.5 to 275.6 mumol/l. After the first application of the compound (day 8) moderate changes of the urinary components - oxalic acid, Na, K, and chloride - significant changes of Ca were observed, whereas after the second application of the compound (day 9) the values no longer differed from control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Allopurinol; Benzbromarone; Benzofurans; Calcium Oxalate; Circadian Rhythm; Drug Therapy, Combination; Female; Humans; Hydrogen-Ion Concentration; Kidney Calculi; Male; Uric Acid

In a collective of 3899 out-patients, the effect of uric acid reduction of benzbromarone was tested. Ten days after beginning of treatment, a uric acid concentration of 5.1 to 5.7 mg/100 ml had been obtained. Three months after beginning of therapy, uric acid values were at 4.9 mg/100 ml, independently of age and sex. As side-effects were observed:diarrhoea in 1% (n = 41) of the treated patients, furthermore, 0,8% (n = 31) complained of gastro-intestinal trouble such as pressure over the stomach, nausea, sensation of fullness and epigastric pain. Only in 2 of the 3899 patients (0.05%) the appearance of a renal colic was observed.

Topics: Benzbromarone; Benzofurans; Diarrhea; Female; Gout; Humans; Kidney Calculi; Male; Nausea; Uric Acid

Topics: Adult; Allopurinol; Anemia; Arthritis; Benzofurans; Gout; Humans; Hyperlipidemias; Hypothyroidism; Hypoxanthines; Kidney Calculi; Male; Metabolism, Inborn Errors; Pedigree; Pentosyltransferases; Uric Acid; Uricosuric Agents

Topics: Benzofurans; Gout; Humans; Kidney Calculi; Uricosuric Agents; Vasodilator Agents