CLOFIBRATE FEEDING TO SPRAGUE-DAWLEY RATS INCREASES ENDOGENOUS BIOSYNTHESIS OF OXALATE AND CAUSES HYPEROXALURIA

The effects of clofibrate feeding (5 g/kg diet) on oxalate metabolism were investigated in male and female rats. Following clofibrate feedin g, 24-hour urinary excretion of oxalate increased until 4 days and the n reached a plateau. Whereas the contribution of dietary oxalate (1.4 g/kg diet, as potassium salt) to urinary oxalate was less than 5% in b oth control and clofibrate-treated male rats, the contribution of diet ary glycolate (1.0 g/kg diet, as sodium salt) to urinary oxalate was s ix times higher in clofibrate-treated male rats compared with controls , indicating that the clofibrate-induced hyperoxaluria is due to incre ased endogenous biosynthesis of oxalate. This was supported by the inc reased lactate dehydrogenase (LDH) activity observed in liver supernat ants of clofibrate-treated rats compared with controls, and the increa sed rate of conversion of glycolate and glyoxylate to oxalate by clofi brate-treated male rat liver supernatants. Female rats had lower excre tion of urinary oxalate and lower levels of liver glycolic acid oxidas e (GAG) as compared with males. Clofibrate-treated female rat liver su pernatants had higher LDH levels and produced more oxalate from glyoxy late. Thus, it can be concluded that the increase in LDH activity may be the cause of the increased endogenous biosynthesis of oxalate leadi ng to increased urinary excretion of oxalate in male and female rats t reated with clofibrate. Copyright (C) 1997 by W.B. Saunders Company.