THE EFFECTS OF BILE-ACIDS ON FRESHLY ISOLATED RAT GLOMERULI AND PROXIMAL TUBULAR FRAGMENTS

The role of bile acids in post-surgical acute renal failure in jaundic ed patients is obscure. In this study the effects of 11 bile acids wer e assessed on freshly isolated rat glomeruli and proximal tubular frag ments using de novo protein synthesis and lactate dehydrogenase (LDH) leakage as markers of cytotoxicity. Lithocholic acid inhibited protein synthesis from 5 mu M, chenodeoxycholic and deoxycholic acid from 50 mu M (P < 0.05). The concentration of hydrophobic bile acids that inhi bited protein synthesis by 50% (IC50) was 10 mu M, 75 mu M and 80 mu M for lithocholic, chenodeoxycholic and deoxycholic acids, respectively . The glycine and taurine conjugates of these bile acids had no signif icant effect on de novo protein synthesis up to 200 mu M. Lithocholic acid (50 mu M), chenodeoxycholic (200 mu M) and deoxycholic acids (200 mu M) caused a significant increase (P < 0.05) in LDH leakage. Lithoc holic acid also directly inhibited LDH activity above 50 mu M (P < 0.0 5), whereas chenodeoxycholic acid and deoxycholic acid had no effect o n LDH below 500 mu M, at which concentration they caused a slight incr ease 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. Hydroph obic bile acids also directly alter LDH activity. Kidney cells are sus ceptible to the hydrophobic bile acids at concentration significantly below their critical micellar concentration. These results suggest tha t both glomeruli and tubules are highly sensitive to hydrophobic bile acids. (C) 1997 Elsevier Science Ltd.