Proteomic analysis of rat plasma by SELDI-TOF-MS under the condition of prevention of progressive adriamycin nephropathy using oral adsorbent AST-120.

AIMS: To determine changes in relative peak intensities of mass-to-charge ratio (m/z) between 2,000 and 15,000, which are difficult to evaluate by 2-dimensional gel electrophoresis, SELDI-TOF-MS (surface-enhanced laser desorption/ionization time of flight-mass spectrometry) proteomic changes in rat models of adriamycin nephropathy with or without AST-120 were investigated. METHODS: A normal group (n = 5), an adriamycin nephropathy group (n = 9), and an adriamycin nephropathy + AST-120 group (4 g/head/day) (n = 9) were established in SD rats. Anion exchange chips, Q10, washed by 50 mM Tris-HCl pH 8 as a ProteinChip and sinapinic acid were used. The mass range between 2,000 and 15,000 Da was measured. Twenty to 34 weeks after adriamycin 3 mg/kg injection, the adriamycin nephropathy + AST-120 group (plasma creatinine value: 2.1 +/- 0.8 mg/dl) clearly demonstrated slight renal dysfunction compared with that in the adriamycin nephropathy group (5.4 +/- 2.0 mg/dl). RESULTS: The relative intensities in the adriamycin nephropathy group were significantly higher in 7 peaks (such as 8,640, and 8,822 Da) and lower in 8 peaks (such as 4,188, and 8,358 Da) than those in the normal group. The relationship between the relative intensity of peaks and the plasma creatinine value demonstrated a positive correlation in 11 peaks (such as 8,640, and 8,822 Da), and a negative correlation in 6 peaks (such as 4,188 and 8,358 Da). Although the relative intensities of peaks in the adriamycin nephropathy + AST-120 group were between that of the adriamycin nephropathy group and that of the normal group, the relative intensities of 4 peaks (such as 3,664 and 5,179 Da) in the adriamycin nephropathy + AST-120 group demonstrated higher values than in the two other groups. The m/z 3,664 peak was purified and identified as a C-terminal fragment of apolipoprotein C-III. CONCLUSION: Low-molecular proteins and peptides in plasma in this chronic renal failure model showed not only increases but also decreases in some peaks. The relative intensities in some peaks increased in the adriamycin nephropathy + AST-120 group more than in the two other groups. One of these peaks was identified as the apolipoprotein C-III fragment. The relationship between these changes and the prevention of progression of chronic renal failure by AST-120 remains to be established.

Effect of oral adsorbent (AST-120) on renal function, acquired renal cysts and aortic calcification in rats with adriamycin nephropathy.

AIMS: The effect of oral adsorbent, AST-120, on the experimental renal disease induced by adriamycin, uninephrectomy and high protein diet proposed as a model of acquired cystic disease of the kidney was investigated. METHODS: 3 mg of adriamycin was injected into the tail vein of rats and 4 weeks later right-side nephrectomy was performed, 2 weeks thereafter 26 rats with urinary protein excretion between 100 and 358 mg/day were selected from 60 rats. Two groups, 13 rats in each group, namely the AST-120-treated group and control group, both of which had equal renal damage before the administration of AST-120 or placebo. AST-120 (0.4 g/100 g BW/day) was administered for 19 weeks. RESULTS: Serum creatinine and BUN in the AST-120-treated group were significantly lower (serum creatinine: 3.3 +/- 2.1 vs. 7.1 +/- 2.7 mg/dl, p < 0.003) and creatinine clearance was higher (0.62 +/- 0.49 vs. 0.29 +/- 0.30 ml/min, p < 0.05) at the final examination than in the control group. Survival rate which was examined using another set of 9 rats was higher in AST-120-treated rats than in AST-120-untreated rats. Serum indoxyl sulfate was significantly lower at all times after using AST-120 in the AST-120-treated group than in contrast to the control group. Histological examination revealed less severe interstitial and cystic changes in the AST-120-treated group. This suggests that AST-120 can prevent or retard the development of acquired renal cystic disease in this model. Aortic calcification tended to be less severe in the AST-120-treated group because of less serum Ca x P products. CONCLUSION: The AST-120-treated group significantly decreased serum creatinine and increased creatinine clearance with less severe renal cystic changes in this model during the later weeks of administration of AST-120 or at death, accompanied with the tendency of less severe aortic calcification.