Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of AST-120 was examined in the rat model of CRF induced by adriamycin (ADM), which is known to induce focal glomerular sclerosis (GS). ADM (2mg/kg) was injected intravenously twice at a 3-wk interval. After 14 wks, rats were paired with control (C) and AST-120 (A) groups according to levels of BUN and proteinuria. Then, the rats were fed regular rat chow with (A, n = 10) or without (C, n = 10) AST-120. After 28 wks, there were more GS in C. Averaged sclerosis index (SI, 0-4 scale) in C was 1.97 (0.94-3.22), while 1.61 (0.60-2.97) in A. When GS was advanced in C (SI > 2.0), largely ameliorated SI was noted in A (2.61 vs. 1.97, C vs. A, p < 0.05 by paired W-test, n = 5 each). Also, in these rats, BUN, serum creatinine and Ht were all improved in A (p < 0.05). Thus, AST-120 was effective in CRF rats induced by ADM when uremia was advanced. The data also indicates that a reduction of uremic toxins could improve glomerular histology and renal function in CRF.
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PMID:[Effect of oral adsorbent (AST-120) in the rat model of chronic renal failure induced by adriamycin]. 128 5

The effects of oral adsorbent, AST-120 (Kureha Chemical Ind. Co., Tokyo), were studied in the rat model of subtotal nephrectomy. In 34 female Sprague-Dawley rats, three quarters of the renal mass were removed from the left kidney by ligation of 3 branches of the left renal artery. One week later, the right kidney was removed. Two days after right nephrectomy, control rats were fed standard rat chow ad libitum, while AST-120-treated rats were fed standard rat chow containing AST-120 ad libitum. The animals were observed for 9 weeks. Of the control rats, some became severely ill and appeared to be almost dying before 9 weeks, while paired AST-120-treated rats appeared well. Body weight was maintained better in AST-120-treated rats than in control rats. At completion of the study, levels of BUN and serum creatinine were lower and glomerular filtration rate and renal plasma flow rate were higher in AST-120-treated than in control rats (p < 0.05), although there was no statistically significant difference in proteinuria. Serum uremic peak 2a measured by high-performance liquid chromatography, which is considered to correspond to uremic toxins, was statistically lower in AST-120-treated rats (p < 0.05). Finally, a marked reduction in the degree of glomerular sclerosis was noted in AST-120-treated versus control rats (p < 0.05). The results indicate that AST-120 is effective in the treatment of chronic renal failure in terms of reducing uremic symptoms as well as preserving renal function and glomerular architecture. The data also indicate that a reduction in uremic toxins could delay the progressive damage of renal function and glomerular architecture in chronic renal failure.
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PMID:Effects of oral adsorbent in the rat model of chronic renal failure. 143 44

Progression of renal insufficiency was evaluated in partially nephrectomized Sprague-Dawley rats at the age of 10 weeks, fed on the low (6%), usual (20%), and high (36%) protein diet (group 6C, 20C, and 36C). Effects of oral adsorbent AST-120 on these experimental uremic models were also examined (group 6A, 20A, 36A). All the rats underwent paired feeding, and survived during the experimental period of 3 weeks. GFR (inulin clearance) and RPF (para-amino hippurate clearance), as well as Ccr was measured before the sacrifice. Initial serum creatinine and Ccr were 1.7 mg/dl and 0.27 ml/min. The rats of group 36C showed progressive elevation of serum creatinine level and decrease in Ccr. At the end of the study, GFR was significantly lower in group 36C than in group 6C and 20C (0.19, 0.68, 0.87 ml/min respectively). Significant elevation of filtration fraction in group 36C suggested that the decrease in GFR mainly resulted from low RPF. Even in group 36C, no glomerular sclerosis was histologically demonstrated in the remnant kidney, and the mean planar area of the remnant glomeruli was significantly small, which might reflect low RPF. Tubulo-interstitial changes like dilatation of the urinary space and tubular epithelial flattening were prominent in group 36C. Beneficial effect of AST-120 was obvious in high protein diet groups. GFR and RPF were rather well preserved in group 36A (0.36 and 0.78 ml/min) with normal filtration fraction. Tubulo-interstitial damage was evidently mild in group 36A. These data suggested the presence of some humoral factors, which can be adsorbed by AST-120 in gastrointestinal tract, and responsible for the deterioration of renal function and tubulo-interstitial damage induced by high protein diet in the uremic condition. Besides hyperfiltration and glomerular hypertrophy, such humoral factors as suggested in this study may contribute to the progression of chronic renal failure to some extent.
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PMID:[Effect of oral adsorbent AST-120 in rats with chronic renal failure--mechanism of progression of renal failure by dietary protein]. 163 28

We studied the effect on the progression of glomerular sclerosis of two different experimental maneuvers, peritoneal dialysis and oral adsorbent, which remove circulating substances in different fashions. Munich-Wistar rats with established glomerular sclerosis, verified by renal biopsy analysis at seven weeks after subtotal nephrectomy, were treated for four weeks with either peritoneal dialysis (PD) or oral charcoal adsorbent (AST-120). Treatment was initiated at eight weeks. Rats were paired in treatment and control groups according to the similarity in the degree of sclerosis determined at biopsy with a minimum of 50 glomeruli analyzed. Systolic blood pressure and BUN and creatinine clearance, measured at seven to eight weeks, were not different among groups. In Group 2 rats, PD was performed with 1.5% dextrose for eight one-hour cycles, six days per week, while Group 1 control rats had zero indwelling time of the dialysate. Group 4 rats received AST-120, an oral adsorbent charcoal, mixed 5% by weight with standard rat chow and given ad libitum from 8 to 12 weeks after subtotal nephrectomy, while control Group 3 rats received only rat chow. Whole kidney GFR at 12 weeks was significantly higher in Group 2 PD versus Group 1 control (0.50 +/- 0.08 vs. 0.30 +/- 0.05 ml/min, P less than 0.05). There was no statistical difference for BUN and whole kidney creatinine or inulin clearance in Group 4 AST-120 treated versus Group 3 control rats. Light microscopic studies in autopsy specimens revealed that both PD and AST-120 attenuated progression of glomerular sclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role for "uremic toxin" in the progressive loss of intact nephrons in chronic renal failure. 178 46

Oral adsorbent (AST-120) reduces blood levels of urea and creatinine in experimental studies. It has also been shown to retard the progression of chronic renal failure in clinical studies. In the present study, the effect of AST-120 was examined in the rat model of subtotal nephrectomy (sNPX). This experimental model of chronic renal failure is characterized by glomerular hyperfunction, glomerular hypertrophy, increased mesangial trapment of macromolecules and subsequent glomerular sclerosis. We report the effect of AST-120 on glomerular hyperfunction, glomerular hypertrophy and mesangial trapment of macromolecules in the early stage and glomerular function and histology in the late stage of the rat model of sNPX. From 2 days after sNPX, rats were fed regular rat chow with (AST group: AST) or without (control) AST-120. At 2 weeks, iron dextran (ID) was injected intravenously. Three days after the injection, mesangial trapment of ID was largely ameliorated in AST when compared with control (p less than 0.02). The value of mean planar area of glomerulus (PAmean) in AST was significantly lower than that in control (p less than 0.05). At 2 and 9 weeks, the values of GFR and RPF in AST were all statistically higher than those in control. At 9 weeks, whereas average glomerular sclerosis index (SI: 0-4 scale) was 1.07 in control, significantly lower SI (0.57) was noted in AST (p less than 0.05). Thus, AST-120 has effects on glomerular hypertrophy, increased mesangial trapment of macromoleculus and finally the progression of chronic renal failure in the rat model of sNPX. The effects are not through reducing glomerular hyperfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effects of oral adsorbent (AST-120) in the experimental model of chronic renal failure--pathophysiological study on renal function, glomerular hypertrophy, mesangial function and glomerular histology]. 226 21

In order to examine the mechanism by which the oral carbonaceous adsorbent, AST-120 delays the appearance of glomerular sclerosis, experiments were carried out in 120 male Sprague-Dawley rats weighing 285-320 g. The rats were first subjected to 2/3, 3/4, and 4/5 nephrectomy (n = 40). The experiments were begun at 2 weeks after the surgery, and were performed over an 8-week period. Half of each group (n = 20) was administered 1 g/day of liquid AST-120, and the other half received liquid vehicle solution with pair feeding in each group. In the 2/3 nephrectomized group the administration of AST-120 delayed the occurrence of glomerular hypertrophy and prevented the appearance of glomerular sclerosis without any significant differences in renal function, systemic blood pressure (SBP), and urinary protein excretion (U-P). In the 3/4 nephrectomized group the administration of AST-120 delayed the appearance of glomerular hypertrophy and sclerosis with significant decreases in SBP and U-P. In the 4/5 nephrectomized group the administration of AST-120 delayed the appearance of glomerular sclerosis and prevented a decrease in renal function. It is concluded that administration of the oral adsorbent AST-120 delays the occurrence of glomerular sclerosis by delaying the appearance of glomerular hypertrophy, systemic hypertension, and the increase in proteinuria. It can be therefore mentioned that the accumulating substances in the digestive tract worsen the abnormal milieu of chronic renal failure.
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PMID:Correction by oral adsorbent of abnormal digestive tract milieu in rats with chronic renal failure. 756 81

To determine the role of indoxyl sulfate in the progression of glomerular sclerosis, the serum level of indoxyl sulfate was measured in patients with uremia, and the effect of oral administration of indoxyl sulfate on renal function and renal histology was studied in subtotally nephrectomized uremic rats. Further, the effects of a low-protein diet and oral sorbent (AST-120) administration on the serum and urine levels of indoxyl sulfate were studied in different groups of subtotally nephrectomized uremic rats. We noted a marked elevation of serum level of indoxyl sulfate in the patients with uremia. The oral administration of indoxyl sulfate to the uremic rats increased the serum creatinine and blood urea nitrogen levels and decreased creatinine clearance, inulin clearance, and p-aminohippuric acid clearance. The glomerular sclerosis index in the indoxyl sulfate-administered uremic rats was higher than in the control uremic rats. A low-protein diet and AST-120 administration decreased the serum and urine levels of indoxyl sulfate, the blood urea nitrogen level, the urinary protein level, and the glomerular sclerosis index in the uremic rats as compared with those on a high-protein diet. Thus, indoxyl sulfate, a circulating uremic toxin, stimulated the progression of glomerular sclerosis in the uremic model. A low-protein diet and AST-120 reduced the serum and urine levels of indoxyl sulfate and suppressed the progression of glomerular sclerosis.
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PMID:Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis. 803 8

To elucidate the mechanisms by which factors in the digestive tract influence the progressive chronic renal failure in rats, we employed the oral adsorbent, AST-120, which can adsorb certain uremic toxins in the gastrointestinal fluid. Administration of AST-120 firstly delayed the appearance of systemic hypertension, secondly delayed the increase in the amount of urinary protein excretion, and finally delayed the emergence of glomerular hypertrophy and glomerulosclerosis. The data obtained did not provide evidence for an inhibitory effect of AST-120 on hypertension. Our results therefore suggest that a pressor substance or its precursor exists in the digestive tract of rats with chronic renal failure.
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PMID:Influence of factors in the digestive tract on the progression of chronic renal failure. 833 93

In order to examine the initiation time of drug treatment for chronic renal failure by the removal of certain substances which are accumulated in the digestive tract, experiments were carried out on 60 male Sprague-Dawley rats weighing 285-325g. The rats were first subjected to 2/3, 3/4 and 4/5 nephrectomy (n = 20). The experiments were begun at 2 weeks after the surgery, and were performed over an 8-week period. Half of each group of nephrectomized rats (n = 10) was administered the oral adsorbent, 1 g/day of Kremezin (AST-120, Kureha Chemical Industry Co, Tokyo), and pair feeding was done in each group of nephrectomized rats. The administration of Kremezin delayed the occurrence of glomerular hypertrophy, glomerulosclerosis, hypertrophy of the glomerular epithelial cells, flattening of the tubular cells, dilation of the tubular cavity and infiltration of monocytes into the interstitium in the 2/3 nephrectomized rats. In addition, the administration of Kremezin delayed the appearance of proteinaceous cast formation in the tubules, ballooning of the tubular cells, an increase in systemic blood pressure and an increase in urinary protein excretion in the 3/4 and 4/5 nephrectomized rats. These findings indicated that the correction of an abnormal milieu within the digestive tract in chronic renal failure can delay its progression. Since the level of the creatinine clearance in the 2/3 nephrectomized rats was equal to approximately 60% of the creatinine clearance in normal rats, it is suggested that drug treatment for chronic renal failure with Kremezin should be initiated before the level of the creatinine clearance decreases to 60% of creatinine clearance in normal human.
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PMID:[Study on the initiation time of drug treatment for chronic renal failure]. 837 90

We have recently demonstrated that indoxyl sulfate promotes the progression of glomerular sclerosis in uremic rats. In the present study, we determined whether an oral adsorbent (AST-120) could reduce the serum and urine levels of indoxyl sulfate and suppress the progression of chronic renal failure (CRF) in undialyzed uremic patients. Twenty-five undialyzed uremic patients were given AST-120 at a dose of 6 g/day for 6 months, while 10 undialyzed uremic patients were not given AST-120. The effects of the oral adsorbent on the slope of the 1/serum creatinine (Scr)-time plot, and the serum and urine levels of indoxyl sulfate were evaluated. Administration of AST-120 significantly decreased the serum and urine levels of indoxyl sulfate, and tended to improve the slope of the 1/SCr-time plot in the CRF patients. Among the patients in whom urinary excretion of indoxyl sulfate was reduced by AST-120, the oral adsorbent significantly improved the slope of the 1/SCr-time plot. The change in the slope of the 1/SCr-time plot showed a significant negative correlation with the change in the urine level of indoxyl sulfate. Thus, patients who showed a greater decrease of urinary indoxyl sulfate also showed more marked suppression of the progression of CRF. These results support the notion that indoxyl sulfate, a protein metabolite, is involved in the progression of CRF, and that an oral adsorbent can delay progression at least partly by reducing the serum and urine levels of indoxyl sulfate.
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PMID:The protein metabolite hypothesis, a model for the progression of renal failure: an oral adsorbent lowers indoxyl sulfate levels in undialyzed uremic patients. 935 Jun 73


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