Comparative vascular effects of levetiracetam and valproate with hyperhomocysteinemia in rat models

Objectives: Hyperhomocysteinemia (HHcy) a significant risk factor for vascular disease, often emerges in epilepsy with the use of antiepileptic drugs. In this relationship, our study investigates the combined effects of HHcy and antiepileptics on vascular function using a rat model.Methods: Fourty two rats were included and divided into six groups as, 1-Control, 2-L-Met, 3-LEV injected, 4-LEV-injected + L-Met, 5-VAL-injected, 6-VAL injected + L-Met. L-Methionine (L-Met) was added to drinking water of rats for 1 month to develop HHcy. Simultaneously, intraperitoneal (ip) injections of sodium valproate (VAL) and levetiracetam (LEV) were administered. Effects were comparatively investigated, and noradrenaline (NA), followed by acetylcholine (ACh) and glyceryl trinitrate (GTN) were applied in organ bath system. Agonist doses were expressed as ten base logarithm (M) through 10(-9), 10(-8), 10(-7), 10(-6), 10(-5), 10(-4) mol/L in dose-response graph.Results: NA contractions between LEV and LEV + L-Met groups showed statistical significance (LEV E-max=288.50 +/- 46.54, LEV + L-Met E-max=480.40 +/- 78.83) (p<0.05) however, no significance was observed among the other groups. ACh relaxations between Control-L-Met (Control Inh(max)=12.65 +/- 2.09, L-Met Inh(max)=50.05 +/- 7.43) (p<0.05), and Control-Val + L-Met (Control E-max=328.20 +/- 52.83, VAL + L-Met E-max=452.60 +/- 71.53) (p<0.01), groups showed statistical significance. Between other groups, no significance was observed. In GTN relaxations, no statistical significance was observed.Conclusions: This study highlights the adverse impact of HHcy on aortic relaxation. Further impairment was observed with VAL compared to other treatment and control groups. These findings underscore the importance of considering vascular side effects when selecting antiepileptic drugs. Ultimately, our study contributes valuable insights that may aid the choice of appropriate treatment strategies to mitigate potential vascular complications of HHcy.