The effect of boric acid on penicillin induced experimental epilepsy

Mustafa Karademir; Gökhan Arslan

doi:10.7197/223.vi.543145

TR EN

Borik asidin penisilin ile indüklenen deneysel epilepsi üzerine etkisi

Öz

Amaç: Günlük hayatta insanlar, bir bor bileşiği olan borik aside maruz kalmaktadırlar. Bu çalışmada, düşük dozlarda uygulanan borik asidin penisilin kaynaklı epileptiform aktivite üzerindeki etkisini araştırdık. Ayrıca, borik asidin gabapentinin antikonvülsan etkisindeki rolünü de inceledik.

Yöntem: Bu çalışmada, kırk sekiz adet erkek Wistar sıçanı kullanıldı. Üretan anestezisinden sonra, sıçanlar stereotaksi aletine bağlandı. Elektrokortikografi kayıtları için sol somatomotor korteks üzerine bir bipolar elektrot sabitlendi. İlk deney setinde, intrakortikal penisilin (500 IU) enjeksiyonundan 30 dakika sonra, dört farklı borik asit dozu (5, 10, 20 ve 40 mg/kg) intraperitoneal olarak uygulandı. İkinci deney setinde, borik asit (20 mg / kg), gabapentin (200 mg/kg) ve borik asit (20 mg/kg) + gabapentin (200 mg/kg) kombinasyonu uygulandı. İlaç enjeksiyonlarından sonra 120 dakika boyunca elektrokortikografi kayıtları kaydedildi ve sonrasında spike frekans ve amplitüdleri hesaplandı.

Bulgular: 5 mg/kg dozunda uygulanan borik asit, kontrol grubuyla karşılaştırıldığında spike frekansını anlamlı ölçüde değiştirmedi. 10, 20 ve 40 mg / kg'lık dozlarında uygulanan borik asit ise, sırasıyla 50., 30. ve 30. dakikalarda ortalama spike frekansını artırarak prokonvülsan aktivite gösterdi. Gabapentin 30. dakikadan sonra ortalama spike frekansını azalttı. 20 mg/kg dozunda uygulanan borik asit, gabapentinin antikonvülsan etkisini inhibe etti. Spike amplüdü açısından hiçbir grup arasında anlamlı fark bulunmadı.

Sonuç: Bu çalışma, borik asidin düşük dozlarının penisilin kaynaklı nöbetleri arttırdığını göstermektedir. Borik asit, bu prokonvulzan etkisini muhtemelen GABAerjik sistem üzerinden göstermektedir.

Anahtar Kelimeler

Epilepsi,Epileptiform aktivite,Penisilin,Gabapentin,Borik asit,Gabapentin

The effect of boric acid on penicillin induced experimental epilepsy

Abstract

Objective: In daily life, people are exposed to a boron compound, boric acid. This study was designed to investigate the effect of different low doses of boric acid on penicillin-induced epileptiform activity. The role of boric acid in the anticonvulsant effect of gabapentin was also researched.

Method: Forty-eight Male Wistar rats were used in this study. After uretan anesthesia, rats were attached to a stereotaxic device. A bipolar electrode was fixed over the left somatomotor cortex for electrocorticography (ECoG) recordings. In the first set of experiments, 30 min after intracortical injection of penicillin (500 IU), four different doses of boric acid were received (5, 10, 20 and 40 mg/kg) intraperitoneally (i.p.). In the second set of experiments, boric acid (20 mg/kg), gabapentin (200 mg/kg) and boric acid (20 mg/kg) + gabapentin (200 mg/kg) combination were administered. Electrocorticography recordings were persisted for 120 minutes after the drug injections and spike frequencies and amplitudes were calculated.

Results: Boric acid, at a dose of 5 mg/kg, did not significantly change the means of spike frequency when compared to the control group. At the doses of 10, 20 and 40 mg/kg, boric acid showed proconvulsant activity by increasing the mean spike frequency in the 50, 30 and 30 minutes, respectively. Gabapentin decreased the means of spike frequency in 30 min. Boric acid (20 mg/kg) inhibited the anticonvulsant effect of gabapentin. No significant difference detected between any groups in terms of spike amplitude.

Conclusions: The results of the present study show that low doses of boric acid increase penicillin-induced seizures. We suggested that boric acid may show its proconvulsant effect probably via GABAergic pathway.

Keywords

Epilepsy,Epileptiform activity,Penicillin,Boric acid,Gabapentin

Kaynakça

World Health Organization; Jan, 2009. Epilepsy Fact Sheet No 999, 2009.
Schachter SC. Seizure disorders. Med Clin North Am. 2009; 93(2):343–351.
Biziere K, Chambon JP. Animal models of epilepsy and experimental seizures. Rev. Neurol 1987; 143: 329-40.
Nielsen FH. Is boron nutritionally relevant? Nutr Rev. 2008; 66(4):183–91.
Naghii MR, Wall PM, Samman S. The boron content of selected foods and the estimation of its daily intake among free-living subjects. J Am Coll Nutr 1996; 15(6):614-9.
Woods, WG. An introduction to boron: History,sources, uses and chemistry. Environ. Health Perspect 1994; 102: 5-11.
Sobel JD, Chaim W, Nagappan V, Leaman D. Treatment of vaginitis caused by Candida glabrata: Use of topical boric acid and flucytosine. Am J Obstet Gynecol 2003 Nov; 189(5): 1297-1300.
O'Sullivan K, Taylor M. Chronic boric acid poisoning in infants. Archives of Disease in Childhood, 1983; 58: 737-749.

International Programme on Chemical Safety, Environmental Health Criteria 204: Boron. WHO (World Health Organisation) 1998; Geneva, Switzerland.
Colak S, Geyikoglu F, Keles ON, Turkez H, Topal A, Unal B. The neuroprotective role of boric acid on aluminum chloride-induced neurotoxicity. Toxicology and Industrial Health 2011; 27(8) 700–710.
Hunt CD. Dietary Boron is a Physiological Regulator of the Normal Inflammatory Response. Trace Elem Man Anim. 2006; 233(March):1071–6.
Sogut I, Oglakci A, Kartkaya K, Ol KK, Sogut MS, Kanbak G, et al. Effect of boric acid on oxidative stress in rats with fetal alcohol syndrome. Exp Ther Med. 2015; 9(3):1023-27.
Kızılay Z, Erken HA, Çetin NK, Aktaş S, Abas Bİ, Yılmaz A. Boric acid reduces axonal and myelin damage in experimental sciatic nerve injury. Neural Regen Res. 2016; 11(10):1660–5.
Gordon AS, Prichard JS, Freedman MH. Seizure disorders and anemia associated with chronic borax intoxication. Can Med Assoc J. 1973; 108(6):719-21.
Sills GJ. The mechanisms of action of gabapentin and pregabalin. Current Opinion in Pharmacology 2006; 6:108–113.
Borowicz KK, Swiader M, Luszczki J. Effect of gabapentin on the anticonvulsant activity of antiepileptic drugs against electroconvulsions in mice: An isobolographic analysis. Epilepsia 2002; 43(9): 956-963.
Comi AM, Traa BS, Mulholland JD, Kadam SD, Johnston MV. Gabapentin Neuroprotection and Seizure Suppression inImmature Mouse Brain Ischemia. Pediatr Res. 2008 Jul; 64(1): 81–85.
Pahl MV, Culver BD, Strong PL, Murray FJ, Vaziri ND. The effect of pregnancy on renal clearance of boron in humans: a study based on normal dietary intake of boron. Toxicol Sci 2001; 60:252–256.
Wong LC, Heimbach MD, Truscorr DR, et al. Boric acid poisoning: report of 11 cases. Can Med Assoc J.1964; 90: 1018-23.Weir RJ, Fisher RS. Toxicologic studies on borax and boric acid. Toxicol Appl Pharmacol 1972; 23:351–364.
Hubbard SA. Comparative toxicology of borates. Biol Trace Elem Res 1998; 66:343–357.
Kar F, Hacıoğlu C, Özkoç M, Üstünışık N, Bütün A, Uslu S, Kanbak G. The New Perspective Neuroprotective Effect Of Boric Acid Against Ethanol-Induced Oxidative Damage On Synaptosome. Journal of Applied Biological Sciences 2018; 12 (2): 28-33.
Hacıoğlu C, Kar F, Sentürk H, Kanbak G. Neuroprotective effects of boric acid against fluoride toxicity on rat synaptosomes. Medical Science and Discovery 2018; 5(7):260-66.
Taylor CP, Gee NS, Su T-Z, Kocsis JD, Welty DF, Brown JP, Dooley DJ, Boden P, Singh L. A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res 1998; 29:233-249.
Taylor CP, Vartanian MG, Andruszkiewicz R, Silverman RB. 3-alkyl GABA and 3-alkylglutamic acid analogues: two new classes of anticonvulsant agents. Epilepsy Res 1992, 11:103-110.
Gotz E, Feuerstein TJ, Lais A, Meyer DK. Effects of gabapentin on release of gamma-aminobutyric acid from slices of rat neostriatum. Arzneim-Forsch 1993; 43: 636-638.
Honmou O, Kocsis JD, Richerson GB. Gabapentin potentiates the conductance increase induced by nipecotic acid in CA1 pyramidal neurons in vitro. Epilepsy Res 1995; 20:193-202.
Leach JP, Sills GJ, Butler E, Forrest G, Thompson GG, Brodie MJ: Neurochemical actions of gabapentin in mouse brain. Epilepsy Res 1997; 27:175-180.
Bicho RC, Gomes SI, Soares AM, Amorim MJ. Non-avoidance behaviour in enchytraeids to boric acid is related to the GABAergic mechanism. Environ Sci Pollut Res Int. 2015; 22(9): 6898-903.
Gong P, Guan X, Pirooznia M, Liang C, Perkins EJ. Gene expression analysis of CL-20-induced reversible neurotoxicity reveals GABA(A) receptors as potential targets in the earthworm Eisenia fetida. Environ Sci Technol 2012; 46:1223–1232.