Mechanism of oral absorbent AST-120 in lipid abnormalities in experimentaluremic rats

Background. We have reported that oral sorbent AST-120 (AST) is effective i n delaying the induction of dialysis in patients with chronic renal failure (CRF) because of its effect on lipid metabolism. To clarify the precise me chanism of AST in lipid abnormalities in CRF, we examined the effect of AST on plasma lipid profile, total bile acids (TBA), and lipoprotein lipase (L PL) activity in experimental uremic rats. Methods. Uremic rats were prepared using male Wistar rats by ligating 5/6 o f the renal artery. Uremic rats were randomly divided into two groups as fo llows: a control group in which rats were maintained on the standard diet a nd an AST group in which rats were maintained on a diet containing 5 g of A ST per 100 g of standard diet for 10 weeks, Plasma LPL activity was measure d as free fatty acid (FFA) generation after intravenous administration of h eparin, Results. Plasma creatinine at 1.5 +/- 0.1 mg/dl was lower in the AST group than the 1.9 +/- 0.5 mg/ml level in the control group. AST significantly de creased plasma total cholesterol from 192 +/- 29 to 142 +/- 25 mg/dl, trigl ycerides from 198 +/- 71 to 99 +/- 38 mg/dl, and TBA from 19.6 +/- 2.6 mu m ol/liter to 8.8 +/- 3.5 mu mol/ml. Plasma LPL activity at 0.22 +/- 0.01 mu mol FFA/min/hr was significantly higher in the AST group than 0.15 +/- 0.03 mu mol FFA/min/hr in the control group. Conclusions, These results suggest that AST may improve plasma lipid abnorm alities by binding to bile acids in the intestinal lumen and preventing the ir reabsorption and inhibiting the: reduction of LPL activity in experiment al uremic rats.