Wilson, EL and Garton, M and Fuller, HR (2016) Anti-epileptic drugs and bone loss: phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells. Epilepsy Research. ISSN 1872-6844

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Abstract

Phenytoin is an antiepileptic drug used in the management of partial and tonic-clonic seizures. In previous studies we have shown that valproate, another antiepileptic drug, reduced the amount of two key bone proteins, pro-collagen I and osteonectin (SPARC, BM-40), in both skin fibroblasts and cultured osteoblast-like cells. Here we show that phenytoin also reduces pro-collagen I production in osteoblast-like cells, but does not appear to cause a decrease in osteonectin message or protein production. Instead, a 24 h exposure to a clinically relevant concentration of phenytoin resulted in a dose-dependent change in electrophoretic mobility of osteonectin, which was suggestive of a change in post-translational modification status. The perturbation of these important bone proteins could be one of the mechanisms to explain the bone loss that has been reported following long-term treatment with phenytoin.

Item Type: Article
Uncontrolled Keywords: epilepsy, drug therapy; phenytoin; valproate; collagen; osteonectin; SPARC; AEDs; anti-epileptic drugs; bone
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Symplectic
Date Deposited: 11 Mar 2016 12:04
Last Modified: 07 Jul 2017 10:54
URI: http://eprints.keele.ac.uk/id/eprint/1554

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