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Chronic use of new generations antiepileptic drugs on bone structure in rats

To investigate the histologic effects of topiramate (TPM), lamotrigine (LTG), levetiracetam (LEV), lacosamide (LCM), clobazam (CLB), and zonisamide (ZNS) on rat bone. Seventy male Wistar-Albino rats (aged 21-24 days, weighing 46.4-55.3 g) were divided into 7 experimental groups with 10 rats each: Control group, TPM group (40 mg/kg/day), LTG group (10 mg/kg/day), LEV group (200 mg/kg/day), LCM group (30 mg/kg/day), CLB group (50 mg/kg/day), and ZNS group (100 mg/kg/day). All the drugs were administered for 90 days. The specimens were analyzed using apoptosis (TUNEL) and immunohistochemical staining. The number of osteoblasts and the thickness of femoral compact bone decreased significantly in TPM, LTG, LEV, LCM, CLB, and ZNS groups. In osteoblasts, there was local atrophy in TPM, LEV, and LCM groups, while intense atrophy was observed in LTG, CLB, and ZNS groups. In all experimental groups, there were abnormally prominent enlargements in the Havers and Volkmann canals. The number of TUNEL-positive cells was higher in all experimental groups compared to the control group, and this difference was statistically significant in CLB and ZNS groups (p<0.001 for both). The HSCORE increased significantly for C-3, C-9, and BAX immunohistochemical staining and increased significantly in TPM, LTG, LEV, LCM, CLB, and ZNS groups Long-term treatment with TPM, LTG, LEV, LCM, CLB, and ZNS until the end of the growth period causes apoptosis and negative effects on rat bone structure.
Keywords: Antiepileptic use, bone health, rats