Carvacrol mitigates proconvulsive effects of lipopolysaccharide, possibly through the hippocampal cyclooxygenase-2 inhibition
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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 (400 μg/kg; i.p.) four hours before the PTZ (80 mg/kg; i.p.) injection. Carvacrol was injected (100 mg/kg; i.p.) immediately after the LPS injection. Following the PTZ injection, behavioral seizures were observed for 30 min. 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.
KeywordsConvulsion Epilepsy ELISA Monoterpenes Neuroinflammation Pentylenetetrazol
This research was supported by Arak University of Medical Sciences. There are no conflicts of interests for the authors.
- Barbalho PG, Lopes-Cendes I, Maurer-Morelli CV (2016) Indomethacin treatment prior to pentylenetetrazole-induced seizures downregulates the expression of il1b and cox2 and decreases seizure-like behavior in zebrafish larvae. BMC Neurosci 17:12. https://doi.org/10.1186/s12868-016-0246-y CrossRefPubMedPubMedCentralGoogle Scholar
- Citraro R, Leo A, Marra R, De Sarro G, Russo E (2015) Antiepileptogenic effects of the selective COX-2 inhibitor etoricoxib, on the development of spontaneous absence seizures in WAG/Rij rats. Brain Res Bull 113:1–7. https://doi.org/10.1016/j.brainresbull.2015.02.004 CrossRefPubMedGoogle Scholar
- Dati LM, Ulrich H, Real CC, Feng ZP, Sun HS, Britto LR (2017) Carvacrol promotes neuroprotection in the mouse hemiparkinsonian model. Neuroscience 356:176–181. https://doi.org/10.1016/j.neuroscience.2017.05.013 CrossRefPubMedGoogle Scholar
- Holtman L, van Vliet EA, van Schaik R, Queiroz CM, Aronica E, Gorter JA (2009) Effects of SC58236, a selective COX-2 inhibitor, on epileptogenesis and spontaneous seizures in a rat model for temporal lobe epilepsy. Epilepsy Res 84:56–66. https://doi.org/10.1016/j.eplepsyres.2008.12.006 CrossRefPubMedGoogle Scholar
- Kovacs Z, Dobolyi A, Juhasz G, Kekesi KA (2014) Lipopolysaccharide induced increase in seizure activity in two animal models of absence epilepsy WAG/Rij and GAERS rats and long Evans rats. Brain Res Bull 104:7–18. https://doi.org/10.1016/j.brainresbull.2014.03.003 CrossRefPubMedGoogle Scholar
- Temp FR, Marafiga JR, Milanesi LH, Duarte T, Rambo LM, Pillat MM, Mello CF (2017) Cyclooxygenase-2 inhibitors differentially attenuate pentylenetetrazol-induced seizures and increase of pro- and anti-inflammatory cytokine levels in the cerebral cortex and hippocampus of mice. Eur J Pharmacol 810:15–25. https://doi.org/10.1016/j.ejphar.2017.05.013 CrossRefPubMedGoogle Scholar
- Zareie P, Sadegh M, Palizvan MR, Moradi-Chameh H (2018) Anticonvulsive effects of endocannabinoids; an investigation to determine the role of regulatory components of endocannabinoid metabolism in the Pentylenetetrazol induced tonic- clonic seizures. Metab Brain Dis 33:939–948. https://doi.org/10.1007/s11011-018-0195-5 CrossRefPubMedGoogle Scholar