(D)-penicillamine increases hepatic oxalate production resulting in hyperoxaluria

Abstract

Purpose: To determine whether (D)-penicillamine is effective in reducing hepatic oxalate production and urinary oxalate excretion.

Materials and methods: (D)-Penicillamine was administered orally to rats to determine its effect on urinary oxalate excretion and used in isolated rat hepatocytes to investigate the effect of (D)-penicillamine on oxalate production from glycolate. Studies involving hepatic aminotransferases and hepatocytes isolated from (D)-penicillamine treated rats were used to clarify the discrepancy between the in vitro and in vivo results.

Results: In hepatocytes (D)-penicillamine lead to a significant reduction in oxalate production from glycolate. In vivo however. (D)-penicillamine led to a significant increase in urinary oxalate excretion and a decrease in plasma aminotransferase activity. Hepatic aminotransferases are involved in diverting oxalate precursors from oxalate production. In vitro, (D)-penicillamine was shown to inhibit hepatic aminotransferases. Hepatocytes isolated from (D)-penicillamine-treated rats produced significantly more oxalate than controls.

Conclusions: These results indicate that (D)-penicillamine increases hepatic oxalate production and urinary oxalate excretion. (D)-penicillamine therefore has no therapeutic potential for reducing endogenous oxalate production and urinary oxalate excretion. Moreover, in conditions such as Wilson's Disease which is often associated with hypercalcuria, its use may be contraindicated.