Histological and immunohistochemical study on the effect of valporic acid on the bone of adult male guinea pigs and the possible protective role of L-carnitine

Abstract

Background: Valporic acid (VPA) is a broad-spectrum antiepileptic drug and is effective in the treatment of different types of epileptic seizures. It usually affects bone and mineral metabolism and increase the risk of fractures due to decreased bone mineral density (BMD). Among dietary supplements, L-carnitine is an emergic candidate with potential bone protective effects. It promotes energy utilization and is important for tissues with high energy requirements.Objective: The target of this work is to estimate the effect of valproic acid on the femur and the possible protective effect of L-carnitine administration in adult male guinea pigs.Materials & Methods: Forty adult male guinea pigs were utilized in the current study. The guinea pigs were divided into four groups, Group I (control group), Group II(L-carnitine treated group), Group III (Valporic acid treated group) and Group IV (L-carnitine and valporic acid treated group). After 10 weeks, the upper parts of femur were processed for histological, morphological and immunohistochemical studies.Results: Valporic acid treated group was associated with enhanced bone turnover as evident by a significant change in serum levels of calcium, osteocalcin and TRAP. Moreover, there was a significant decrease in trabecular and cortical bone thickness and a significant change in the mean number of osteoclasts and osteoblasts. Histologically, evidence of bone resorption was manifested in the femoral bone with resorption cavities, irregular endosteal surface. Decrease of collagen in the cortical bone was evident in trichrome-stained sections. Immunohistochemically, this group showed positive immunoreactivity for caspase-3 in osteocytes and decrease in osteopontin expression in bone matrix. L-carnitine supplementation with valporic acid in group IV has ameliorating effect on the histological abnormalities of bone.Conclusion: L-carnitine improved the biochemical, histological and morphometric changes induced by VPA, and therefore, there is a potential benefit in using L-carnitine with long term administration of valporic acid.