Influence of Diphenylhydantoin on Lysosomal Enzyme Release during Bone Resorption in Vitro

Abstract
The effect of diphenylhydantoin (DPH) [an anticonvulsant] 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 .mu.g/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 Hp. The release of the cytosolic enzyme lactate dehydrogenase was not influenced by concentrations of DPH up to 50 .mu.g/ml but higher concentrations caused an increased release indicating cell injury. When bone resorption was stimulated by prostaglandin E2, DPH (50 .mu.g/ml) also reduced the mobilization of bone mineral and the release of .beta.-glucuronidase without influencing the release of lactate dehydrogenase. DPH reduces bone resorption by interfering with cellular release processes.