The effects of Bile Acids on Freshly Isolated Rat Glomeruli and Proximal Tubular Fragments

Abstract

The role of bile acids in post-surgical acute renal failure in jaundiced patients is obscure. In this study the effects of 11 bile acids were assessed on freshly isolated rat glomeruli and proximal tubular fragments using de novo protein synthesis and lactate dehydrogenase (LDH) leakage as markers of cytotoxicity. Lithocholic acid inhibited protein synthesis from 5 μ m, chenodeoxycholic and deoxycholic acid from 50 μ m ( P<0.05). The concentration of hydrophobic bile acids that inhibited protein synthesis by 50% (IC 50) was 10 μ m, 75 μ m and 80 μ m for lithocholic, chenodeoxycholic and deoxycholic acids, respectively. The glycine and taurine conjugates of these bile acids had no significant effect on de novo protein synthesis up to 200 μ m. Lithocholic acid (50 μ m), chenodeoxycholic (200 μ m) and deoxycholic acids (200 μ m) caused a significant increase ( P<0.05) in LDH leakage. Lithocholic acid also directly inhibited LDH activity above 50 μ m ( P<0.05), whereas chenodeoxycholic acid and deoxycholic acid had no effect on LDH below 500 μ m, at which concentration they caused a slight increase in activity. The cytotoxic bile acids had no effect on the level of reactive oxygen species in kidney fragments. Hydrophobic bile acids inhibit protein synthesis and increase membrane permeability. Hydrophobic bile acids also directly alter LDH activity. Kidney cells are susceptible to the hydrophobic bile acids at concentration significantly below their critical micellar concentration. These results suggest that both glomeruli and tubules are highly sensitive to hydrophobic bile acids.