Motomiya Y

Reversibility of adenine-induced renal failure in rats

AbstractBackground. A renal failure model prepared from rats fed on an adenine diet provides valuable information about the pathomechanism of various complications associated with a persistent uremic state. To establish an animal experimental model in which the animals survive in a persistent uremic state, it is essential to settle a point of no return, i.e., an irreversible point. We investigated an irreversible point using the rat renal failure model induced by adenine treatment.nMethods. Rats were fed on a diet containing 0.75% adenine for 2, 4, or 6 weeks, and they were then fed an adenine-free diet for an additional 4 weeks to evaluate the degree of recovery from renal dysfunction.nResults. The rats fed on the adenine diet for 2 weeks showed a decrease in mean serum creatinine(s-Cr) from 1.8 mg/dl before to 0.7 mg/dl after the observation period, with mild anemia. The rats fed on the adenine diet for 4 weeks showed persistent renal dysfunction. Although the mean s-Cr decreased from 2.7 to 2.0 mg/dl, it continued to be higher than the normal range, and the anemia worsened. In the rats fed on the adenine diet for 6 weeks, the mean s-Cr increased from 3.4 to 3.6 mg/dl. Hypoproteinemia was also observed and some animals died.nConclusion. Based on the above results, it was concluded that to prepare a model of chronic renal failure in rats compatible to chronic renal failure seen clinically, the administration of a 0.75% adenine diet for 4 weeks is most appropriate.

Effects of foreign bodies on development of urinary bladder tumors in rats treated with N-butyl-N-(4-hydroxybutyl) nitrosamine

SummaryThe effects of chronic mechanical stimulation induced by glass balls or paraffin balls on precursor lesions of the urinary bladder of male Wistar strain rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in the drinking water were studied.When foreign bodies were present in the bladder, proliferative lesions of the urinary bladder epithelium were found even without administration of carcinogen. When the foreign bodies were implanted into the urinary bladder and then rats were given BBN in the drinking water for the first 4 weeks of the experimental period, a high incidence of tumors of the urinary bladder was observed. The incidence of tumors induced by BBN was increased by the presence of glass balls or paraffin balls in the urinary bladder.These results clearly show that foreign bodies in the urinary bladder have a significant effect in promoting carcinogenesis of the urinary bladder in rats.

Studies on urinary isozymes of lactic dehydrogenase and β-glucuronidase in patients with bladder tumors

SummaryIsozymes of urinary lactic dehydrogenase (LDH) were studied in 55 subjects, including 17 patients with bladder tumors. Normal clear urine from healthy persons showed little activity of LDH5, but in 11 out of 17 patients with bladder tumors LDH5 was increased sufficiently to invert the ratio of LDH5/LDH1,although the urine was not contaminated appreciably with leucocytes. Studies on tissue LDH isozymes in 16 tumor specimens strongly suggested that the increased LDH5 in the urine of patients with bladder tumors originated from the tumors themselves. β-Glucuronidase (β-G) isozymes were studied in urine specimens from 10 normal subjects, and 10 patients with bladder tumors and in 5 specimens of normal epithelium and 5 of tumor tissue. Two or three distinct bands of β-G were separated from specimens of urine and tumor tissue from patients with bladder tumors, but only a single band was found in specimens from normal subjects.

Branched chain amino acid in adenine-induced uremic rats treated with rHuEPO

AbstractBackground. It is well known that chronic renal failure shows an abnormal amino acid profile characterized by a decrease in branched chain amino acid (BCAA).nMethods. To investigate the change in BCAA with uremia and the effect of recombinant human erythropoietin (rHuEPO) on BCAA level, we measured the plasma and muscle levels of BCAA in adenine-induced renal anemia in Wistar rats.nResults. A significant correlation was found between plasma and muscle tissue levels of BCAA. Further, not only the plasma level but the muscle level of each BCAA showed an inverse correlation with the serum creatinine value. Both plasma and muscle BCAA levels showed, in addition, significant recovery after rHuEPO treatment.nConclusions. Taking these results into account, we conclude that the decrease in BCAA is a clinicopathological feature essentially associated with uremia (i.e., it is not an epiphenomenon), and that BCAA levels could be recovered by rHuEPO treatment. However, the pathological mechanism by which BCAA level is decreased in the uremic state and is recovered after rHuEPO treatment remains to be elucidated.