Carbamazepine induces oxidative stress on rats' microvascular endothelial cells of the blood-brain barrier

Aim: Carbamazepine (CBZ) is a commonly used anticonvulsant. Its effect on the blood-brain barrier(BBB) is poorly understood. Hence the current study had investigated the effect of CBZ on the isolated cultured microvascular epithelial cells of albino rats. Oxidative stress was investigated as the underlying mechanism of its cytotoxicity. Material and Method: Albino rats' microvascular endothelial cells (rMVECs) were isolated. CBZ induced cytotoxicity was evaluated by Alamar blue (AB) assay using concentrations range 1-1000 mu M. Oxidative stress markers as lipid peroxidation (TBARS), Catalase, superoxide dismutase(SOD), reduced glutathione(GSH), reactive oxygen species (ROS) were evaluated 24 hours after exposure to CBZ estimated IC50 and 50 mu M. Also, the protective effect of anti-oxidation reduced GSH was studied. Results: AB assay showed that CBZ decreased the viability of the cells in relation to their concentrations and exposure durations. CBZ's 24 hours estimated IC50s was about 130 mu M. CBZ increased TBARS in the both 130 and 50 mu M concentrations (p = 0.0009). CBZ significantly decreased SOD, catalase, and GSH levels in its estimated IC50s, while in the lower concentration (50 mu M) only CBZ showed a significant effect on reduced GSH(p=0.003). Also, CBZ increased significantly (p=0.0018) ROS with both tested concentrations. Addition of reduced GSH significantly decreased the cytotoxic effect of CBZ in its estimated IC50s (p<0.0001) and in the concentration of 50 mu M (p=0.0005). Discussion: CBZ can be cytotoxic to the BBB cells with disruption of its integrity which may expose the nervous system to various harmful circulating molecules. Also, co-administration of antioxidants with CBZ may have a protective role.