Influence of diphenylhydantoin on lysosomal enzyme release during bone resorption in vitro

The effect of diphenylhydantoin (DPH) on the release of lysosomal enzymes during resorption of cultured mouse calvarial bone was studied. The enzyme activities of beta-glucuronidase and beta-galactosidase in the culture medium was taken as indicators for lysosomal enzyme release. In concentrations 50 micrograms/ml or higher, DPH inhibited the release of beta-glucuronidase and beta-galactosidase in parallel with bone resorption as indicated by reduced release of 45Ca, Ca2+, Pi and hydroxyproline. The release of the cytosolic enzyme lactate dehydrogenase was not influenced by concentrations of DPH up to 50 micrograms/ml but higher concentrations caused an increased release indicating cell injury. When bone resorption was stimulated by prostaglandin E2, DPH (50 micrograms/ml) also reduced the mobilization of bone mineral and the release of beta-glucuronidase without influencing the release of lactate dehydrogenase. It is suggested that DPH by interfering with cellular release processes reduces the resorption of bone.