Prenatal toxicity of gabapentin on bone development in rat offsprings

Abstract

Abstract Background Gabapentin is a drug commonly prescribed to adult pregnant women with neuropathic pain and epilepsy. Since the effect of antiepileptic drugs used in pregnant women with epilepsy on prenatal bone development is controversial, this study was conducted to demonstrate the toxic effects of gabapentin use during pregnancy on the skeletal system. Methods In the study, pregnant Wistar albino rats were randomly selected and divided into 5 groups (n = 4) as control and 10 mg/kg/day, 30 mg/kg/day, 60 mg/kg/day and 120 mg/kg/day gabapentin groups. The pups were subjected to double skeletal staining (DSS) and the ossification lengths and areas of the fore and hind bones of the pups were measured. Immunohistochemistry (IHC) was used to evaluate the ossification sites and the levels of alkaline phosphatase (AP) and tartrate resistant acid phosphatase (TRAP) immunoreactivity in the pups' femurs. Results: According to the results, the weights and morphometric sizes of the pups were lower than those of the control group. It was found that ossification rates in the fore and hind bones were statistically significantly lower. It was revealed that AP and TRAP intensities which is metabolic markers for bone development were reduced in the experimental groups compared to the control group. Conclusions We have shown that continuous use of gabapentin during pregnancy in rats results in lower birth weight offspring, delayed ossification in the offspring and adverse effects on bone metabolism as the dose increases.