Combination therapy with dipeptidyl peptidase-4 and P2X7 purinoceptor inhibitors gives rise to antiepileptic effects in rats

Objective(s): Although the available therapeutic agents alleviate the symptoms in patients with temporal lobe epilepsy (TLE), these antiepileptic drugs do not provide adequate control of seizures in 30-40% of patients. This study was conducted to evaluate anti-epileptic effects of simultaneous inhibition of dipeptidyl peptidase-4 and P2 × 7 purinoceptors in Kainate treated rats.

Materials and methods: Brilliant Blue G )BBG(, linagliptin )lin( and lin + BBG were administrated 30 min prior to induction of the intrahippocampal kainate model of epilepsy in male Wistar rats. In the case of valproic acid group, the animals intraperitoneally received valproic acid for 7 consecutive days prior to induction of the model. We carried out histological evaluations, monitoring of behavior, recording of intracranial electroencepholography (IEEG), and determination of astrogliosis and DNA fragmentation using ELISA methods.

Results: Our results showed that BBG and lin combination therapy had better effects on decrease in astrogliosis, DNA fragmentation and cognitive disturbances than ones whereas its effects on neuronal survival and seizure severity was similar to only BBG or lin. Likewise, the effects of lin + BBG on decrease in DNA fragmentation and cognitive disturbances were better than valproic acid group.

Conclusion: Our findings suggest that simultaneous inhibition of dipeptidyl peptidase-4 and P2 × 7 purinoceptors might more efficiently provide protection against progression of the kainate-induced TLE in rats.

Keywords: Dipeptidyl peptidase-4 inhibitor; Neuro protection; P2X7 receptor antagonist; Temporal lobe epilepsy; astrogliosis.