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 synd rome followed by renal failure. This study was designed to determine if an oral adsorbent, AST-120, ameliorates renal lesions and TGF-beta 1 expressio n 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 c ontrol Imai rats. Results. AST-120-administered rats showed significantly lower levels of blo od urea nitrogen, serum creatinine, urinary protein, serum total-cholestero l, serum triglyceride, and serum and urinary indoxyl sulfate: and significa ntly higher levels of serum albumin and creatinine clearance than control r ats. AST-120 reduced the glomerular sclerosis index, interstitial fibrosis area, and the extent of glomerular lipid deposition. Immunohistochemistry d emonstrated that AST-120 reduced the expression of transforming growth fact or (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 re nal failure in the Imai rats by ameliorating glomerular sclerosis and inter stitial fibrosis, accompanied with reduced expression of TGF-beta 1 and TIM P-1, and reduced infiltration of macrophages in the kidneys.