An oral adsorbent ameliorates renal overload of indoxyl sulfate and progression of renal failure in diabetic rats.
Otsuka Long-Evans Tokushima Fatty (OLETF) rats were established as a new model of non-insulin-dependent diabetes mellitus. An oral adsorbent, AST-120, is effective in removing such uremic toxins as indoxyl sulfate and delays the progression of chronic renal failure (CRF). This study was designed to determine the effects of AST-120 on the progression of CRF in uninephrectomized OLETF (1/2NxOLETF) rats and the localization of indoxyl sulfate in their kidneys. Four weeks after unilateral nephrectomy, 14 OLETF rats were divided into two groups; AST-120-administered and control 1/2NxOLETF rats. Long-Evans Tokushima Otsuka rats, which are genetically similar to the OLETF rats but not diabetic, were also included. After the administration of AST-120 for 36 weeks, we examined the effects of AST-120 on renal functional and pathological changes in the three groups. The control 1/2NxOLETF rats showed marked hyperglycemia, hyperlipidemia, renal failure, glomerular sclerosis, and tubulointerstitial injury. The administration of AST-120 to the 1/2NxOLETF rats retarded the progression of renal dysfunction and fibrosis, as well as hyperlipidemia, and reduced serum and urinary levels of indoxyl sulfate. Immunohistochemistry showed that AST-120 markedly reduced the overload of indoxyl sulfate in tubular epithelial cells, especially dilated tubules, of the 1/2NxOLETF rats. In conclusion, AST-120 delayed the progression of renal failure and fibrosis in 1/2NxOLETF rats and decreased the overload of indoxyl sulfate on renal tubular cells.
Aoyama
I
I
Nagoya University Daiko Medical Center, Nagoya, Japan.
Niwa
T
T
D000284:Administration, Oral; D000818:Animals; D001806:Blood Urea Nitrogen; D002244:Carbon / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D018450:Disease Progression; D007150:Immunohistochemistry; D007200:Indican / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D010087:Oxides / Q000494:pharmacology*; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D010087:Oxides; D014280:Triglycerides; D002244:Carbon; C040896:AST 120; D002784:Cholesterol; D003404:Creatinine; D007200:Indican