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 feeding, 24-hour urinary excretion of oxalate increased until 4 days and then 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 both control and clofibrate-treated male rats, the contribution of dietary glycolate (1.0 g/kg diet, as sodium salt) to urinary oxalate was six times higher in clofibrate-treated male rats compared with controls, indicating that the clofibrate-induced hyperoxaluria is due to increased endogenous biosynthesis of oxalate. This was supported by the increased lactate dehydrogenase (LDH) activity observed in liver supernatants of clofibrate-treated rats compared with controls, and the increased rate of conversion of glycolate and glyoxylate to oxalate by clofibrate-treated male rat liver supernatants. Female rats had lower excretion of urinary oxalate and lower levels of liver glycolic acid oxidase (GAO) as compared with males. Clofibrate-treated female rat liver supernatants had higher LDH levels and produced more oxalate from glyoxylate. Thus, it can be concluded that the increase in LDH activity may be the cause of the increased endogenous biosynthesis of oxalate leading to increased urinary excretion of oxalate in male and female rats treated with clofibrate.
Sharma
V
V
Department of Surgery, University of Erlangen, Germany.
Schwille
P O
PO
D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D002994:Clofibrate / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006959:Hyperoxaluria / Q000209:etiology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D010070:Oxalates / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D014545:Urinary Calculi / Q000453:epidemiology
D010070:Oxalates; D000429:Alcohol Oxidoreductases; D007770:L-Lactate Dehydrogenase; C020821:glycollate oxidase; D002994:Clofibrate