Effects of melatonin and theanine administration on pentylenetetrazole-inducedseizures and brain tissue oxidative damage in ovariectomized rats

Background/aim: The effects of coadministration of melatonin and theanine (Mel/Thea) on pentylenetetrazole (PTZ)-induced seizures and brain tissue oxidative damage were investigated in ovariectomized (OVX) and sham-operated rats. Materials and methods: The rats were divided into the following groups: 1) sham, 2) ovariectomized (OVX), 3) sham-PTZ, 4) OVX-PTZ, 5) sham-Mel/Thea-PTZ, and 6) OVX-Mel/Thea-PTZ. Groups 1-4 received saline, while groups 5 and 6 received a combination of Mel/Thea for 6 weeks. All animals except for those in groups 1 and 2 received a single injection of PTZ. Results: The OVX-PTZ group had higher generalized tonic-clonic seizure (GTCS) latency compared to the sham-PTZ group. Administration of Mel/Thea increased minimal clonic seizure and GTCS latencies in both the sham-Mel/Thea-PTZ and OVX-Mel/Thea-PTZ groups compared to the controls. Additionally, PTZ exposure increased malondialdehyde levels and reduced thiol concentrations in brain tissues of both the sham-PTZ and OVX-PTZ groups. Mel/Thea pretreatment resulted in MDA reduction and thiol increase in brain tissues. Conclusion: The results of this study demonstrated the antioxidant and anticonvulsant activities of Mel/Thea despite the presence or absence of ovarian hormones.

Effects of melatonin and theanine administration on pentylenetetrazole-inducedseizures and brain tissue oxidative damage in ovariectomized rats

Background/aim: The effects of coadministration of melatonin and theanine (Mel/Thea) on pentylenetetrazole (PTZ)-induced seizures and brain tissue oxidative damage were investigated in ovariectomized (OVX) and sham-operated rats. Materials and methods: The rats were divided into the following groups: 1) sham, 2) ovariectomized (OVX), 3) sham-PTZ, 4) OVX-PTZ, 5) sham-Mel/Thea-PTZ, and 6) OVX-Mel/Thea-PTZ. Groups 1-4 received saline, while groups 5 and 6 received a combination of Mel/Thea for 6 weeks. All animals except for those in groups 1 and 2 received a single injection of PTZ. Results: The OVX-PTZ group had higher generalized tonic-clonic seizure (GTCS) latency compared to the sham-PTZ group. Administration of Mel/Thea increased minimal clonic seizure and GTCS latencies in both the sham-Mel/Thea-PTZ and OVX-Mel/Thea-PTZ groups compared to the controls. Additionally, PTZ exposure increased malondialdehyde levels and reduced thiol concentrations in brain tissues of both the sham-PTZ and OVX-PTZ groups. Mel/Thea pretreatment resulted in MDA reduction and thiol increase in brain tissues. Conclusion: The results of this study demonstrated the antioxidant and anticonvulsant activities of Mel/Thea despite the presence or absence of ovarian hormones.

___

  • Sander JW. The epidemiology of epilepsy revisited. Curr Opin Neurol 2003; 16: 165–170.
  • Meador KJ. Cognitive outcomes and predictive factors in epilepsy. Neurology 2002; 58: S21–S26.
  • Halliwell B. Oxygen radicals as key mediators in neurological disease: fact or fiction? Ann Neurol 1992; 32: S10–S15.
  • Sharma J, Sharma A, Bahadur A, Vimala N, Satyam A, Mittal S. Oxidative stress markers and antioxidant levels in normal pregnancy and pre-eclampsia. Int J Gynaecol Obstet 2006; 94: 23–27.
  • El‐Khayat HA, Soliman NA, Tomoum HY, Omran MA, El‐Wakad AS, Shatla RH. Reproductive hormonal changes and catamenial pattern in adolescent females with epilepsy. Epilepsia 2008; 49: 1619–1626.
  • Finocchi C, Ferrari M. Female reproductive steroids and neuronal excitability. Neurol Sci 2011; 32: 31–35.
  • Harden CL. Sexuality in men and women with epilepsy. CNS Spectr 2006; 11: 13–18.
  • Murialdo G, Magri F, Tamagno G, Ameri P, Camera A, Colnaghi S, Perucca P, Ravera G, Galimberti CA. Seizure frequency and sex steroids in women with partial epilepsy on antiepileptic therapy. Epilepsia 2009; 50: 1920–1926.
  • Rhodes ME, Frye CA. Androgens in the hippocampus can alter, and be altered by, ictal activity. Pharmacol Biochem Behav 2004; 78: 483–493.
  • Juneja LR, Chu DC, Okubo T, Nagato Y, Yokogoshi H. L-Theanine—a unique amino acid of green tea and its relaxation effect in humans. Trends Food Sci Technol 1999; 10:
  • Kakuda T. Neuroprotective effects of the green tea components theanine and catechins. Biol Pharm Bull 2002; 25: 1513–1518.
  • Nathan PJ, Lu K, Gray M, Oliver C. The neuropharmacology of L-theanine (N-ethyl-L-glutamine) a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother 2006; 6: 21–30.
  • Park SK, Jung IC, Lee WK, Lee YS, Park HK, Go HJ, Kim K, Lim NK, Hong JT, Ly SY et al. A combination of green tea extract and l-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study. J Med Food 2011; 14: 334–343.
  • Dawson D, Encel N. Melatonin and sleep in humans. J Pineal Res 1993; 15: 1–12.
  • Banach M, Gurdziel E, Jêdrych M, Borowicz KK. Melatonin in experimental seizures and epilepsy. Pharmacol Rep 2011; 63: 1–11.
  • Bonnefont-Rousselot D, Collin F. Melatonin: action as antioxidant and potential applications in human disease and aging. Toxicology 2010; 278: 55–67.
  • Reiter RJ. Functional pleiotropy of the neurohormone melatonin: antioxidant protection and neuroendocrine regulation. Front Neuroendocrinol 1995; 16: 383–415.
  • Yamamoto HA, Tang HW. Preventive effect of melatonin against cyanide-induced seizures and lipid peroxidation in mice. Neurosci Lett 1996; 207: 89–92.
  • Luboshitzky R, Lavie P. Melatonin and sex hormone interrelationships--a review. J Pediatr Endocrinol Metab 1999; 12: 355–362.
  • Okatani Y, Morioka N, Wakatsuki A. Changes in nocturnal melatonin secretion in perimenopausal women: correlation with endogenous estrogen concentrations. J Pineal Res 2000; 28: 111–118.
  • Abd-Allah ARA, El-Sayed ESM, Abdel-Wahab MH, Hamada FMA. Effect of melatonin on estrogen and progesterone receptors in relation to uterine contraction in rats. Pharmacol Res 2003; 47: 349–354.
  • Alaei H, Hosseini M. Angiotensin converting enzyme inhibitor captopril modifies conditioned place preference induced by morphine and morphine withdrawal signs in rats. Pathophysiology 2007; 14: 55–60.
  • Hosseini M, Alaei HA, Havakhah S, Neemati Karimooy HA, Gholamnezhad Z. Effects of microinjection of angiotensin II and captopril to VTA on morphine self-administration in rats. Acta Biol Hung 2009; 60: 241–252.
  • Hosseini M, Alaei HA, Headari R, Eslamizadeh MJ. Effects of microinjection of angiotensin II and captopril into nucleus accumbens on morphine self-administration in rats. Indian J Exp Biol 2009; 47: 361–367.
  • Hosseini M, Sharifi MR, Alaei H, Shafei MN, Karimooy HA. Effects of angiotensin II and captopril on rewarding properties of morphine. Indian J Exp Biol 2007; 45: 770–777.
  • Saffarzadeh F, Eslamizade MJ, Nemati Karimooy HA, Hadjzadeh MA, Khazaei M, Hosseini M. The effect of L-arginine on Morris water maze tasks of ovariectomized rats. Acta Physiol Hung 2010; 97: 216–223.
  • Azizi-Malekabadi H, Hosseini M, Saffarzadeh F, Karami R, Khodabandehloo F. Chronic treatment with the nitric oxide synthase inhibitor, L-NAME, attenuates estradiol-mediated improvement of learning and memory in ovariectomized rats. Clinics (Sao Paulo) 2011; 66: 673–679.
  • Azizi-Malekabadi H, Hosseini M, Soukhtanloo M, Sadeghian R, Fereidoni M, Khodabandehloo F. Different effects of scopolamine on learning, memory, and nitric oxide metabolite levels in hippocampal tissues of ovariectomized and sham- operated rats. Arq Neuropsiquiatr 2012; 70: 447–452.
  • Ebrahimzadeh Bideskan AR, Hosseini M, Mohammadpour T, Karami R, Khodamoradi M, Nemati Karimooy H, Alavi H. Effects of soy extract on pentylenetetrazol-induced seizures in ovariectomized rats. Zhong Xi Yi Jie He Xue Bao 2011; 9: 611–618.
  • Hosseini M, Ghasemzadeh RM, Sadeghnia H, Rakhshandeh H. Effects of different extracts of Rosa damascena on pentylenetetrazol-induced seizures in mice. Zhong Xi Yi Jie He Xue Bao 2011; 9: 1118–1124.
  • Hosseini M, Sadeghnia HR, Salehabadi S, Alavi H, Gorji A. The effect of L-arginine and L-NAME on pentylenetetrazole induced seizures in ovariectomized rats, an in vivo study. Seizure 2009; 18: 695–698.
  • Hosseini M, Harandizadeh F, Niazamand S, Soukhtanloo M, Mahmoudabady M. Antioxidant effect of Achillea wilhelmsii extract on pentylenetetrazole (seizure model)-induced oxidative brain damage in Wistar rats. Indian J Physiol Pharmacol 2013; 57: 418–424.
  • Hosseinzadeh H, Sadeghnia HR. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci 2005; 8: 394–399.
  • Khodabandehloo F, Hosseini M, Rajaei Z, Soukhtanloo M, Farrokhi E, Rezaeipour M. Brain tissue oxidative damage as a possible mechanism for the deleterious effect of a chronic high dose of estradiol on learning and memory in ovariectomized rats. Arq Neuropsiquiatr 2013; 71: 313–319.
  • Pourganji M, Hosseini M, Soukhtanloo M, Zabihi H, Hadjzadeh MA. Protective role of endogenous ovarian hormones against learning and memory impairments and brain tissues oxidative damage induced by lipopolysaccharide. Iran Red Crescent Med J 2014; 16: e13954.
  • Sudha K, Rao AV, Rao A. Oxidative stress and antioxidants in epilepsy. Clin Chim Acta 2001; 303: 19–24.
  • Rodrigues AD, Scheffel TB, Scola G, Santos MTD, Fank B, de Freitas SCV, Dani C, Vanderlinde R, Henriques JA, Coitinho AS et al. Neuroprotective and anticonvulsant effects of organic and conventional purple grape juices on seizures in Wistar rats induced by pentylenetetrazole. Neurochem Int 2012; 60:
  • Costello DJ, Delanty N. Oxidative injury in epilepsy: potential for antioxidant therapy? Expert Rev Neurother 2004; 4: 541– 553.
  • Reilly C, Agnew R, Neville BG. Depression and anxiety in childhood epilepsy: a review. Seizure 2011; 20: 589–597.
  • Maldonado A, Ramos W, Pérez J, Huamán L, Gutiérrez E. Convulsive status epilepticus: clinico-epidemiologic characteristics and risk factors in Peru. Neurología 2010; 25: 478–484 (in Spanish with English abstract).
  • Liang L, Beaudoin M, Fritz M, Fulton R, Patel M. Kainate- induced seizures, oxidative stress and neuronal loss in aging rats. Neuroscience 2007; 147: 1114–1118.
  • Czapinski P, Blaszczyk B, Czuczwar SJ. Mechanisms of action of antiepileptic drugs. Curr Top Med Chem 2005; 5: 3–14.
  • Xie T, Wang WP, Mao ZF, Qu ZZ, Luan SQ, Jia LJ, Kan MC. Effects of epigallocatechin-3-gallate on pentylenetetrazole- induced kindling, cognitive impairment and oxidative stress in rats. Neurosci Lett 2012; 516: 237–241.
  • Liu SH, Chang CD, Chen PH, Su JR, Chen CC, Chaung HC. Docosahexaenoic acid and phosphatidylserine supplementations improve antioxidant activities and cognitive functions of the developing brain on pentylenetetrazol- induced seizure model. Brain Res 2012; 1451: 19–26.
  • Bikjdaouene L, Escames G, Leon J, Ferrer JM, Khaldy H, Vives F, Acuña-Castroviejo D. Changes in brain amino acids and nitric oxide after melatonin administration in rats with pentylenetetrazole‐induced seizures. J Pineal Res 2003; 35: 54–60.
  • Yokozawa T, Dong E. Influence of green tea and its three major components upon low-density lipoprotein oxidation. Exp Toxicol Pathol 1997; 49: 329–335.
  • Reiter RJ. Melatonin: lowering the high price of free radicals. Physiology 2000; 15: 246–250.
  • Mohanan P, Yamamoto HA. Preventive effect of melatonin against brain mitochondria DNA damage, lipid peroxidation and seizures induced by kainic acid. Toxicol Lett 2002; 129: 99–105.
  • Borowicz KK, Kamiński R, Gasior M, Kleinrok Z, Czuczwar SJ. Influence of melatonin upon the protective action of conventional anti-epileptic drugs against maximal electroshock in mice. Eur Neuropsychopharmacol 1999; 9: 185–190.
  • Yildirim M, Marangoz C. Anticonvulsant effects of melatonin on penicillin-induced epileptiform activity in rats. Brain Res 2006; 1099: 183–188.
  • Abbasi F, Krumholz A, Kittner SJ, Langenberg P. Effects of menopause on seizures in women with epilepsy. Epilepsia 1999; 40: 205–210.
  • Verrotti A, Latini G, Manco R, De Simone M, Chiarelli F. Influence of sex hormones on brain excitability and epilepsy. J Endocrinol Invest 2007; 30: 797–803.
  • Penovich PE, Helmers S. Catamenial epilepsy. Int Rev Neurobiol 2008; 83: 79–90.
  • Galanopoulou AS, Alm EM, Velíšková J. Estradiol reduces seizure-induced hippocampal injury in ovariectomized female but not in male rats. Neurosci Lett 2003; 342: 201–205.
  • Hoffman G, Moore N, Fiskum G, Murphy A. Ovarian steroid modulation of seizure severity and hippocampal cell death after kainic acid treatment. Exp Neurol 2003; 182: 124–134.
  • Pereira M Jr, Soares JM Jr, Valente SG, Oliveira PB, Cavalheiro EA, Amado D, Baracat EC. Estrogen effects on pilocarpine- induced temporal lobe epilepsy in rats. Maturitas 2009; 62: 190–196.
  • Frye CA. Role of androgens in epilepsy. Expert Rev Neurother 2006; 6: 1061–1075.
  • Reddy DS. Role of neurosteroids in catamenial epilepsy. Epilepsy Res 2004; 62: 99–118.
  • Riazi K, Honar H, Homayoun H, Rashidi N, Dehghani M, Sadeghipour H, Gaskari SA, Dehpour AR. Sex and estrus cycle differences in the modulatory effects of morphine on seizure susceptibility in mice. Epilepsia 2004; 45: 1035–1042.
  • Maguire JL, Stell BM, Rafizadeh M, Mody I. Ovarian cycle– linked changes in GABAA receptors mediating tonic inhibition alter seizure susceptibility and anxiety. Nat Neurosci 2005; 8: 797–804.
  • Kokate T, Cohen A, Karp E, Rogawski M. Neuroactive steroids protect against pilocarpine-and kainic acid-induced limbic seizures and status epilepticus in mice. Neuropharmacology 1996; 35: 1049–1056.
  • Członkowska AI, Krząścik P, Sienkiewicz-Jarosz H, Siemiątkowski M, Szyndler J, Bidziński A, Płaźnik A. The effects of neurosteroids on picrotoxin-, bicuculline-and NMDA-induced seizures, and a hypnotic effect of ethanol. Pharmacol Biochem Behav 2000; 67: 345–353.
  • Jahnke G, Marr M, Myers C, Wilson R, Travlos G, Price C. Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats. Toxicol Sci 1999; 50: 271–279.
  • Karasek M, Kowalski AJ, Zylinska K. Serum melatonin circadian profile in women suffering from the genital tract cancers. Neuro Endocrinol Lett 1999; 21: 109–113.
  • Costa-Lotufo LV, Fonteles MMF, Lima ISP, de Oliveira AA, Nascimento VS, de Bruin VMS, Viana GSB. Attenuating effects of melatonin on pilocarpine-induced seizures in rats. Comp Biochem Physiol C 2002; 131: 521–529.
  • Acufla‐Castroviejo D, Escames G, Macks M, Hoyos AM, Carballo AM, Arauzo M, Montes R, Vives F. Minireview: Cell protective role of melatonin in the brain. J Pineal Res 1995; 19: 57–63.
  • Yahyavi-Firouz-Abadi N, Tahsili-Fahadan P, Riazi K, Ghahremani MH, Dehpour AR. Involvement of nitric oxide pathway in the acute anticonvulsant effect of melatonin in mice. Epilepsy Res 2006; 68: 103–113.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Multidrug resistance and integron carriage in clinical isolates ofPseudomonas aeruginosa in Tehran, Iran

Somayeh Moazami GOUDARZI, Fereshteh EFTEKHAR

Bilateral sympathicotomy for hyperhidrosis without using single-lung ventilation

Tevfik KAPLAN, Perihan EKMEKÇİ, Bülent KOÇER, Serdar HAN

The evaluation of transient hypothyroidism in patients diagnosedwith congenital hypothyroidism

Havva Nur Peltek KENDİRCİ, Zehra AYCAN, Elif SAĞSAK, Melikşah KESKİN, Semra ÇETİNKAYA

Sexuality and sexual dysfunction in spinal cord-injured men in Turkey

Ramazan Yavuz AKMAN, Evrim Coşkun ÇELİK, Metin KARATAŞ

Value of prealbumin in assessment of nutrition for critically ill patients (Reply to Letter to the Editor:)

Mehmet KILIÇ, Levent ÖZTÜRK, Mehmet TOKAÇ, Birkan BOZKURT, Ersin Gürkan DUMLU, Abdussamed YALÇIN, Mesut ÖZDEDEOĞLU

Determining the health beliefs and breast cancer fear levels ofwomen regarding mammography

Fatma ERSİN, Fatma GÖZÜKARA, Perihan POLAT, Gözde ERÇETİN, Mehmet Ekrem BOZKURT

The effect of swimming and type of stroke on bone metabolism in competitiveadolescent swimmers: a pilot study

Sinem AKGÜL, Nuray KANBUR, Şükrü Alpan CİNEMRE, Erdem KARABULUT, Orhan DERMAN

Epidemiological and clinical characteristics and management of oropharyngeal tularemia outbreak

Mustafa Önder UZUN, Keramettin YANIK, Müge ERDEM, Uğur KOSTAKOĞLU, Gürdal YILMAZ, Yeliz Tanriverdi ÇAYCI

Healthy subjects' knowledge of surgical complications: a hospital-based survey

Ersin Gürkan DUMLU, Mehmet KILIÇ, Levent ÖZTÜRK, Mehmet TOKAÇ, Ömer PARLAK, Abdussamed YALÇIN

Urinary incontinence among women registered with a family health center in the Southeastern Anatolia Region and the factors affecting its prevalence

Fatma GÖZÜKARA, İbrahim KORUK, Burcu KARA