EFFECTS OF TRITON WR-1339 AND OROTIC-ACID ON BILIARY AND SERUM DOLICHOLS IN RATS

Two lysosomal storage diseases, aspartylglucosaminuria and mannosidosi s, are associated with highly elevated serum dolichol concentrations. To eludicate possible mechanisms leading to elevated serum dolichols, we studied the effects of Triton WR 1339 (known to increase serum chol esterol) and erotic acid (known to decrease serum cholesterol) on bloo d and biliary dolichol and beta hexosaminidase levels in rats. In Trit on WR 1339-treated rats, serum dolichol was markedly increased compare d with saline-treated controls 1 (400 +/- 70 ng/mL, n = 7 v 85 +/- 11 ng/mL, n = 8, P < .001), 4(789 +/- 70 ng/mL, n = 10 v 110 +/- 10 ng/mL , n = 7, P < .0001), and 8 (549 +/- 43 ng/mL, n = 8 v 87 +/- 8 ng/mL, n = 7, P < .001) days after administration of the drug. By contrast, s erum dolichol was decreased (64 +/- 5 ng/mL, n = 8 v 119 +/- 7 ng/mL, n = 8, P < .0001) after a 7-day erotic acid feeding compared with cont rols. Serum beta-hexosaminidase was unaffected by both treatments. Oro tic acid also increased biliary dolichol (280 +/- 47 ng/100 g body wei ght [BW]/h, n = 7 v 83 +/- 15 ng/100 g BW/h, n = 7, P < .01) and beta- hexosaminidase (21 +/- 3 mU/100 g BW/h, n = 7 v 8.3 +/- 2 mU/100 g BW/ h, n = 9, P < .01) excretion compared with controls. Thus, both Triton WR 1339 and erotic acid have an effect on dolichol metabolism, and it is conceivable-based on our results-that serum dolichol concentration s are regulated, at least in part, by a mechanism similar to that for serum cholesterol levels. Copyright (C) 1998 by W.B. Saunders Company.