Abstract
Borneol, a bicyclic monoterpene, can easily cross the blood brain barrier and was found to possess gamma amino butyric acid (GABA) modulatory effect. The present study was aimed at investigating the antiepileptogenic effect of borneol in the pentylenetetrazole (PTZ)-induced kindling besides its ability to suppress oxidative stress and neuroinflammatory marker, glial fibrillary acidic protein (GFAP). Repeated administration of a subconvulsive dose of PTZ (35 mg/kg, i.p.) on every alternate day for 4 weeks produced kindling in mice. Borneol (5, 10, and 25 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) were given as a pretreatment prior to each PTZ injection during the progression of kindling. Oxidative stress parameters such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and lipid peroxidation (LPO) were assessed at the end of the study. Neuronal damage was assessed by hematoxylin and eosin staining technique. GFAP was also evaluated in the hippocampus region of the brain by using immunohistochemistry. Borneol significantly suppressed the process of epileptogenesis in PTZ-kindled mice. The biochemical alterations induced by PTZ kindling were ameliorated in borneol-treated animals which was indicated by decreased LPO and increased SOD, GSH, CAT levels. The distinct neuronal damage observed in the kindled group was counteracted by borneol. Furthermore, it decreased the levels of GFAP which was manifested by reduced immunostaining. The above results are suggestive of the antiepileptogenic potential of borneol in the PTZ-induced kindling model of epilepsy, and thus, it could be a prospective molecule in the treatment of epilepsy.
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Abbreviations
- PTZ:
-
Pentylenetetrazole
- GFAP:
-
Glial fibrillary acidic protein
- GABA:
-
Gamma aminobutyric acid
- MES:
-
Maximal electroshock
- SOD:
-
Superoxide dismutase
- CAT:
-
Catalase
- GSH:
-
Reduced glutathione
- LPO:
-
Lipid peroxidation
- MDA:
-
Malondialdehyde
References
Aebi H (1974) Catalase. In: Bergmeyer HU (ed) Methods in enzymatic analysis, vol 3. Academic Press Inc, New York, pp. 673–686
Almeida JR, Souza GR, Silva JC, Saraiva SR, Oliveira Júnior RG, Quintans JS, Barreto RS, Bonjardim LR, Cavalcanti SC, Quintans Júnior LJ (2013) Borneol, a bicyclic monoterpene alcohol, reduces nociceptive behavior and inflammatory response in mice. Scientific World Journal. Hindawi Publishing Corporation 1-5
Cavazos JE, Sutula TP (1990) Progressive neuronal loss induced by kindling: a possible mechanism for mossy fiber synaptic reorganization and hippocampal sclerosis. Brain Res 527(1):1–6
Costa LG (1994) Cell signaling and neurotoxic events. In: Chang LW, editor. Principles of neurotoxicology. New York: Marcel Dekker, 475–493.
Dringen R, Gutterer JM, Hirrlinger J (2000) Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur J Biochem 267(16):4912–4916
Franke H, Kittner H (2001) Morphological alterations of neurons and astrocytes and changes in emotional behavior in pentylenetetrazol-kindled rats. Pharmacol Biochem Behav. 70(2–3):291–303
Frantseva MV, Perez Velazquez JL, Tsoraklidis G, Mendonca AJ, Adamchik Y, Mills LR, Carlen PL, Burnham MW (2000) Oxidative stress is involved in seizure-induced neurodegeneration in the kindling model of epilepsy. Neuroscience 97(3):431–435
Granger RE, Campbell EL, Johnston GA (2005) (+)- and (−)-Borneol: efficacious positive modulators of GABA action at human recombinant α1β2γ2L GABAA receptors. Biochem Pharmacol 69(7):1101–1111
Gupta YK, Veerendra Kumar MH, Srivastava AK (2003) Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition and oxidative stress in rats. Pharmacol Biochem Behav. 74(3):579–585
Horváthová E, Slamenová D, Marsálková L, Sramková M, Wsólová L (2009) Effects of borneol on the level of DNA damage induced in primary rat hepatocytes and testicular cells by hydrogen peroxide. Food Chem Toxicol 47(6):1318–1323
Ilhan A, Ahmet G, Ferah A, Suat K, Mustafa I (2005) Antiepileptogenic and antioxidant effects of Nigella sativa oil against pentylenetetrazole induced kindling in mice. Neuropharmacology 49(4):456–464
Ishige K, Schubert D, Sagara Y (2001) Flavonoids protect neuronal cells from oxidative stress by three distinct mechanisms. Free Radic Biol Med 30(4):433–446
Jain S, Bharal N, Khurana S, Mediratta PK, Sharma KK (2011) Anticonvulsant and antioxidant actions of trimetazidine in pentylenetetrazole-induced kindling model in mice. Naunyn-Schmied Arch Pharmacol 383:385–392
Khurgel M, Ivy GO (1996) Astrocytes in kindling: relevance to epileptogenesis. Epilepsy Res 26(1):163–175
Li X (2012) Improved pyrogallol autoxidation method: a reliable and cheap superoxide scavenging assay suitable for all antioxidants. J Agric Food Chem 60(25):6418–6424
Liu R, Zhang L, Lan X, Li L, Zhang TT, Sun JH, Du GH (2011) Protection by borneol on cortical neurons against oxygen-glucose deprivation/reperfusion: involvement of anti-oxidation and anti-inflammation through nuclear transcription factor κappaB signaling pathway. Neuroscience 176:408–419
Löscher W, Schmidt D (2011) Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia 52(4):657–678
Lucindo J, Guimarães A, Araújo B, Oliveira G, Santana M, Moreira F, Santos M, Cavalcanti S, Lucca W, Botelho M, Ribeiro L, Nóbrega F, Almeida R (2010) Carvacrol, (−)-borneol and citral reduce convulsant activity in rodents. Afr J Biotechnol 9(39):6566–6572
Matsuda S, Umeda M, Uchida H, Kato H, Araki T (2009) Alterations of oxidative stress markers and apoptosis markers in the striatum after transient focal cerebral ischemia in rats. J Neural Transm 116(4):395–404
Nandi A, Chatterjee B (1988) Assay of superoxide dismutase activity in animal tissues. J Biosci 13(3):305–315
Okhawa H, Nobuko O, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358
Pohle W, Becker A, Grecksch G, Juhre A, Willenberg A (1997) Piracetam prevents pentylenetetrazol kindling-induced neuronal loss and learning deficits. Seizure 6(6):467–474
Rauca C, Zerbe R, Jantze H (1999) Formation of free hydroxyl radicals after pentylenetetrazole-induced seizure and kindling. Brain Res 847(2):347–351
Reilly CA, Aust SD (1999) Measurement of lipid peroxidation. Curr Protoc Toxicol 2(4):1–13
Saha L, Bhandari S, Bhatia A, Banerjee D, Chakrabarti A (2014) Anti-kindling effect of bezafibrate, a peroxisome proliferator-activated receptors alpha agonist, in pentylenetetrazole induced kindling seizure model. J Epilepsy Res 4(2):45–54
Sakuma M, Hayakawa N, Kato H, Araki T (2008) Time dependent changes of striatal interneurons after focal cerebral ischemia. J Neural Transm 115(3):413–422
Schmidt D (2002) The clinical impact of new antiepileptic drugs after a decade of use in epilepsy. Epilepsy Res 50(1–2):21–32
Sedlak J, Lindsay RH (1968) Estimation of total and non-protein sulfhydryl groups in tissues with Ellman’s reagent. Anal Biochem 25(1):192–205
Sherafat MA, Ronaghi A, Molaei L, Nejadhoseynian M, Ghasemi R, Hosseini A, Naderi N, Motamedi F (2013) Kindling-induced learning deficiency and possible cellular and molecular involved mechanisms. Neurol Sci 34(6):883–890
Silveira e Sá R, LN A, de Sousa D P (2013) A review on anti-inflammatory activity of monoterpenes. Molecules 18(1):1227–1254
Sinha AK (1972) Calorimetric assay of catalase. Anal Biochem 47(2):389–394
Sleven H, Gibbs J, Heales S, Thom M, Cock HR (2006) Depletion of reduced glutathione precedes inactivation of mitochondrial enzymes following limbic status epilepticus in the rat hippocampus. Neurochem Int 48(2):75–82
Smith IK, Vierheller TL, Thorne CA (1988) Assay of glutathione reductase in crude tissue homogenates using 5,5′-dithiobis(2-nitrobenzoic acid). Anal Biochem 175(2):408–413
Weydert CJ, Cullen JJ (2010) Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat Protoc 5(1):51–66
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This work was supported by University grants commission (UGC), New Delhi, India.
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Tambe, R., Jain, P., Patil, S. et al. Antiepileptogenic effects of borneol in pentylenetetrazole-induced kindling in mice. Naunyn-Schmiedeberg's Arch Pharmacol 389, 467–475 (2016). https://doi.org/10.1007/s00210-016-1220-z
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DOI: https://doi.org/10.1007/s00210-016-1220-z