Carvacrol mitigates proconvulsive effects of lipopolysaccharide, possibly through the hippocampal cyclooxygenase-2 inhibition.

Abstract

Systemic injection of LPS changes neuronal excitability and increase susceptibility for convulsions. Carvacrol exerts neuroprotective and antiepileptic effects in animal models. Herein, we investigated the anticonvulsive effect of carvacrol on LPS induced seizure severity and possible involvement of the hippocampal COX-1 and -2 activities in this effect. Adult male wistar rats were used. LPS was injected (400μg/kg; i.p.) four hours before the PTZ (80mg/kg; i.p.) injection. Carvacrol was injected (100mg/kg; i.p.) immediately after the LPS injection. Following the PTZ injection, behavioral seizures were observed for 30min. Latency and duration for each stage were recorded for analysis. Rats divided into seven groups: (1) PTZ, (2) LPS + PTZ, (3) carvacrol + PTZ, (4) LPS + carvacrol + PTZ, (5) LPS, (6) carvacrol, (7) intact. At the end of the experimental procedure the hippocampus of all animals were extracted to measure COX- 1 and 2 levels using the ELISA. LPS injection four hours before the PTZ injection were significantly reduced latency to seizure stages 3-5 and increased duration of the stage 5 in compare with PTZ group (p < 0.05). Carvacrol significantly reduced these effects of LPS on seizure susceptibility (p < 0.05). However, injection of carvacrol alone before the PTZ injection did not significantly affect seizure indexes in compare with PTZ group. Additionally, LPS significantly increased hippocampal level COX-2 but not COX-1 (p < 0.01) and carvacrol significantly attenuates this effect of LPS (p < 0.001). Carvacrol prevents the proconvulsant effect of LPS possibly through the inhibition of the COX-2 increased activity.