Investigation of the Effect of Propolis on Penicillin Induced Epileptiform Activity in Rats

Abstract

Aim: The aim of this study was to investigate the effects of propolis (PP), which has antioxidant and neuroprotective effects, on penicillin-induced epileptiform activity in rats. Material and Methods: Forty-two adult male Wistar rats were divided into 6 groups as control (CONT), penicillin (PEN), diazepam (DZM), only propolis (OPP), 50 mg/kg propolis (PP50), and 100 mg/kg propolis (PP100). ECoG recording was taken from rats. At the end of the experiment, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were determined from serum samples. Moreover, the latency of the first epileptiform activity, spike-wave frequency (SWF), and spike-wave amplitude (SWA) of the epileptiform activity were analyzed. Results: The latency of the DZM and PP100 groups was found to be longer than the CONT groups. The time-dependent SWF and total SWF of the PP50 and PP100 groups were lower than the CONT group. No significant difference was found between the groups in terms of SWA. SOD, CAT, and GPx levels were found to be higher, but the MDA level was lower in PP50 and PP100. Conclusion: As a result, propolis may be a potential antiepileptic drug candidate in the future with its antioxidant activity as well as prolonging latency and reducing SWF in epilepsy models.

Keywords

• Epilepsy
• Propolis
• Oxidative Stress
• Penicillin
• Electrocorticography

References

1. Beghi E. The epidemiology of epilepsy. Neuroepidemiology. 2020;54:185-91.
2. Kanner AM, Bicchi MM. Antiseizure medications for adults with epilepsy. JAMA. 2022;327:1269.
3. Beyazcicek E, Ankarali S, Beyazcicek O, et al. Effects of thymoquinone, the major constituent of Nigella sativa seeds, on penicillin-induced epileptiform activity in rats. Neurosciences. 2016;21:131-7.
4. Armstead WM, Mirro R, Leffler CW, et al. Cerebral superoxide anion generation during seizures in newborn pigs. J Cereb Blood Flow Metab. 1989;9:175-9.
5. Cárdenas-Rodríguez N, González-Trujano ME, Aguirre-Hernández E, et al. Anticonvulsant and antioxidant effects of Tilia americana var. mexicana and flavonoids constituents in the pentylenetetrazole-induced seizures. Oxid Med Cell Longev. 2014;2014:329172.
6. Sudha K, Rao A V., Rao A. Oxidative stress and antioxidants in epilepsy. Clin Chim Acta. 2001;303:19-24.
7. Ankaralı S, Beyazçiçek E, Ankaralı H, et al. The effect of rapamycin on penicillin- induced epileptiform activity in rats: an electrophysiological study. Anatolian Clinic the Journal of Medical Sciences. 2016;21:197-206.
8. Zulhendri F, Perera CO, Tandean S. Can propolis be a useful adjuvant in brain and neurological disorders and injuries? A systematic scoping review of the latest experimental evidence. Biomedicines. 2021;9:1227.

9. Kalia A, Morya S, Bioactives ANJ of F, et al. Health from the hive: therapeutic potential of propolis-a review. J Food Bioact. 2022;18:77-84.
10. Ndreu L, Hurben AK, Nyman GSA, et al. Investigation into propolis components responsible for inducing skin allergy: air oxidation of caffeic acid and its esters contribute to hapten formation. Chem Res Toxicol. 2023;36:859-69.
11. Ahangari Z, Naseri M, Vatandoost F. Propolis: chemical composition and its applications in endodontics. Iran Endod J. 2018;13:285-92.
12. Braakhuis A. Evidence on the health benefits of supplemental propolis. Nutrients. 2019;11:2705.
13. Przybyłek I, Karpiński TM. Antibacterial properties of propolis. Molecules. 2019;24:2047.
14. Tolba MF, Azab SS, Khalifa AE, et al. Caffeic acid phenethyl ester, a promising component of propolis with a plethora of biological activities: A review on its anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective effects. IUBMB Life. 2013;65:699-709.
15. Morsy FA, El Din AAG, Farrag ARH, et al. Protective effect of fish liver oil and propolis on anticonvulsant drugs-induced osteoporosis. J Arab Soc Med Res. 2014;9:81-9.
16. Kaya ST, Agan K, Fulden-Agan A, et al. Protective effect of propolis on myocardial ischemia/reperfusion injury in males and ovariectomized females but not in intact females. J Food Biochem. 2022;46:e14109.
17. Zingue S, Nde CBM, Michel T, et al. Ethanol-extracted Cameroonian propolis exerts estrogenic effects and alleviates hot flushes in ovariectomized Wistar rats. BMC Complement Altern Med. 2017;17:65.
18. Ögün MN, Çetinkaya A, Beyazçiçek E. The effect of vortioxetine on penicillin-induced epileptiform activity in rats. Arq Neuropsiquiatr. 2019;77:412-7.
19. Kaya GB, Emre MH. Effects of propolis on spatial memory induced by lithium pilocarpine in the experimental status epilepticus model in the rats. Journal of Natural Sciences Research. 2019;9:18.
20. Marquele FD, Stracieri KM, Fonseca MJ V, et al. Spray-dried propolis extract. I: physicochemical and antioxidant properties. Pharmazie. 2006;61:325-30.
21. Mannaa F, El-Shamy KA, El-Shaikh KA, et al. Efficacy of fish liver oil and propolis as neuroprotective agents in pilocarpine epileptic rats treated with valproate. Pathophysiology. 2011;18:287-94.
22. Shahin NN, Shamma RN, Ahmed IS. A nano-liposomal formulation of caffeic acid phenethyl ester modulates Nrf2 and NF-κβ signaling and alleviates experimentally induced acute pancreatitis in a rat model. Antioxidants. 2022;11:1536.
23. Mitić BP, Mitić DM, Radić MS, et al. Honeybee propolis phenol, caffeic acid phenethyl ester, attenuates cisplatin-induced kidney damage – a multitarget approach. Records of Natural Products. 2022;16:293-306.
24. Dos Santos FF, Morais-Urano RP, Cunha WR, et al. A review on the anti-inflammatory activities of Brazilian green, brown and red propolis. J Food Biochem. 2022;46:e14350.
25. Eşrefoğlu M, Gül M, Ateş B, et al. The ultrastructural and biochemical evidences of the beneficial effects of chronic caffeic acid phenethyl ester and melatonin administration on brain and cerebellum of aged rats. Fundam Clin Pharmacol. 2009;24:305-15.
26. Dichter M a, Ayala GF. Cellular mechanisms of epilepsy: a status report. Science. 1987;237:157-64.
27. Erfanparast A, Tamaddonfard E. Effects of intracortical microinjection of vitamin B12 on penicillin-induced epileptiform activity in rats. Acta Neurobiol Exp (Wars). 2015;75:200-7.
28. Arık AE, Bağırıcı F, Sefil F, Marangoz C. Effect of levetiracetam on penicillin induced epileptic activity in rats. Acta Neurobiol Exp (Wars). 2014;74:266-75.
29. Wallace KL. Antibiotic-induced convulsions. Crit Care Clin. 1997;13:741-62.
30. Carmona-Aparicio L, Zavala-Tecuapetla C, González-Trujano ME, et al. Status epilepticus: using antioxidant agents as alternative therapies. Exp Ther Med. 2016;12:1957-62.
31. Ilhan A, Iraz M, Gurel A, et al. Caffeic acid phenethyl ester exerts a neuroprotective effect on CNS against pentylenetetrazol-induced seizures in mice. Neurochem Res. 2004;29:2287-92.
32. Zárraga-Galindo N, Vergara-Aragón P, Rosales-Meléndez S, et al. Effects of bee products on pentylenetetrazole-induced seizures in the rat. Proc West Pharmacol Soc. 2011;54:33-40.
33. Karayel B. The Investigation of the effect of propolis on the acetylcholinesterase and oxidative stress in the brain of mouse model of experimental epilepsy model. Ph.D. thesis. Van Yüzüncü Yıl University, Van, 2019.
34. Mohamed WAM, Ismail T, Farouk S. The ameliorative potential of ethanolic extract of propolis on hematotoxicity and structural neuronal damage in hyperthermia-exposed rats. Iran J Basic Med Sci. 2016;19:875-82.
35. Türkez H, Yousef MI, Geyikoglu F. Propolis prevents aluminium-induced genetic and hepatic damages in rat liver. Food Chem Toxicol. 2010;48:2741-6.
36. Goel R, Saxena P. Pycnogenol protects against pentylenetetrazole-induced oxidative stress and seizures in mice. Curr Clin Pharmacol. 2019;14:68-75.
37. Ilhan A, Aladag MA, Kocer A, et al. Erdosteine ameliorates PTZ-induced oxidative stress in mice seizure model. Brain Res Bull. 2005;65:495-9.
38. Obay BD, Taşdemir E, Tümer C, et al. Dose dependent effects of ghrelin on pentylenetetrazole-induced oxidative stress in a rat seizure model. Peptides. 2008;29:448-55.
39. Eraković V, Zupan G, Varljen J, Simonić A. Pentylenetetrazol-induced seizures and kindling: changes in free fatty acids, superoxide dismutase, and glutathione peroxidase activity. Neurochem Int. 2003;42:173-8.
40. Akbas SH, Yegin A, Ozben T. Effect of pentylenetetrazol-induced epileptic seizure on the antioxidant enzyme activities, glutathione and lipid peroxidation levels in rat erythrocytes and liver tissues. Clin Biochem. 2005;38:1009-14.