Oral adsorbent ameliorates renal TGF-beta 1 expression in hypercholesterolemic rats.
BACKGROUND
A spontaneously hypercholesterolemic Imai rat has recently been reported as a model of focal glomerulosclerosis that causes nephrotic syndrome followed by renal failure. This study was designed to determine if an oral adsorbent, AST-120, ameliorates renal lesions and TGF-beta 1 expression in the rats.


METHODS
AST-120 was given orally to the Imai rats for 32 weeks, and renal function and pathology were compared between the AST-120-administered and control Imai rats.


RESULTS
AST-120-administered rats showed significantly lower level of blood urea nitrogen, serum creatinine, urinary protein, serum total-cholesterol, serum triglyceride, and serum and urinary indoxyl sulfate, and significantly higher levels of serum albumin and creatinine clearance than control rats. AST-120 reduced the glomerular sclerosis index, interstitial fibrosis area, and the extent of glomerular lipid deposition. Immunohistochemistry demonstrated that AST-120 reduced the expression of transforming growth factor (TGF)-beta 1 and tissue inhibitor of metalloproteinase (TIMP)-1 as well as interstitial infiltration of macrophages in the renal cortex of the Imai rats.


CONCLUSIONS
AST-120 prevented the progression of nephrotic syndrome and renal failure in the Imai rats by ameliorating glomerular sclerosis and interstitial fibrosis, accompanied with reduced expression of TGF-beta 1 and TIMP-1, and reduced infiltration of macrophages in the kidneys.
Aoyama
I
I
Nagoya University Daiko Medical Center, Japan.
Miyazaki
T
T
Takayama
F
F
Tsukushi
S
S
Saga
S
S
Shimokata
K
K
Niwa
T
T
D000284:Administration, Oral; D000818:Animals; D001806:Blood Urea Nitrogen; D002244:Carbon / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D006937:Hypercholesterolemia / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D007678:Kidney Glomerulus / Q000737:chemistry; D008297:Male; D010087:Oxides / Q000494:pharmacology*; D011507:Proteinuria / Q000517:prevention & control / Q000652:urine; D051381:Rats; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D010087:Oxides; D016212:Transforming Growth Factor beta; D014280:Triglycerides; D002244:Carbon; C040896:AST 120; D002784:Cholesterol; D003404:Creatinine