Abstract
A range of bone abnormalities including short stature have been reported to be associated with the use of antiepileptic drugs (AEDs) in children. Exactly how AEDs impact skeletal growth, however, is not clear. In the present study, rat growth plate chondrocytes were cultured to study the effects of AEDs, including valproic acid (VPA), oxcarbazepine (OXA), levetiracetam (LEV), lamotrigine (LTG), and topiramate (TPM) on the skeletal growth. VPA markedly reduced the number of chondrocytes by apoptosiswhile other AEDs had no effect. The apoptosis associated noncleaved and cleaved caspase 3, and caspases were increased by exposure to VPA, which up-regulated cyclooxygenase 2 (COX-2) mRNA and protein levels likely through histone acetylation. The COX-2 inhibitor NS-398 attenuated the effects of VPA up-regulating COX-2 expression and decreased VPA-induced caspase 3 expression. The use of VPA in children should be closely monitored or replaced, where appropriate, by AEDs which do not apparently affect the growth plate chondrocytes.
Highlights
Epilepsy is a chronic condition characterized by the recurrence of seizures not provoked by a metabolic or toxic disease or fever [1]
A dose-response experiment conducted over a concentration range of 0–600 μg/mL for 5 days of consecutive daily valproic acid (VPA) treatments showed a significant decrease range of 0–600 μg/mL for 5 days of consecutive daily VPA treatments showed a significant decrease in in chondrocyte number over the dose range, with a statistically significant effect being demonstrated chondrocyte number over the dose range, with a statistically significant effect being demonstrated at at the lowest dose used (30 μg/mL) (Figure 2)
As cyclooxygenase 2 (COX-2) is a major proinflammatory signaling molecule that is involved in regulating chondrocyte chondrocyte apoptosis, we investigated whether VPA treatment regulated the COX-2 expression of apoptosis, we investigated whether VPA treatment regulated the COX-2 expression of rat growth rat growth plate chondrocytes in our system
Summary
Epilepsy is a chronic condition characterized by the recurrence of seizures not provoked by a metabolic or toxic disease or fever [1]. Seizures can spontaneously remit in some cases, lifelong antiepileptic drug (AED) treatment is always necessary for those with refractory epilepsy [5]. This creates a medical dilemma as prolonged AED administration is associated with a number of undesirable side effects including endocrine and metabolic disorders, psychiatric and behavioral disorders, and drug interaction side effects [6,7,8]. The diagnosis and treatment of epilepsy most commonly occur in childhood when bone growth is at its maximum. Public Health 2020, 17, 3675; doi:10.3390/ijerph17103675 www.mdpi.com/journal/ijerph
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