Possible Nitric Oxide Mechanism Involved in the Protective Effect of L-theanine on Haloperidol-Induced Orofacial Dyskinesia

10.4103/CJP.CJP_8_19

Cheng-Chia Tsai；Mao-Hsien Wang；Kuo-Chi Chang；Hung-Sheng Soung；Chih-Chuan Yang；Hsiang-Chien Tseng

Haloperidol ； L-theanine ； nitric oxide ； orofacial dyskinesia ； striatum

The Chinese Journal of Physiology

62卷1期（2019 / 02 / 28）

17 - 26

英文

Having powerful antioxidative properties, L-theanine (LT), one of the major amino acid components in green tea, has potent anti-oxidative and neuroprotective effects. In this study, we examined the potential protective effects of LT on haloperidol (HAL)-induced orofacial dyskinesia (OD) in rats. HAL treatment (1 mg/kg intraperitoneally for 21 days) induced OD; significant increases (P ＜ 0.001) in the frequency of vacuous chewing movement and tongue protrusion as well as the duration of facial twitching. LT treatment (100 mg/kg orally for 35 days, starting 14 days before HAL injection) was able to prevent most of the HAL-induced OD. LT treatment was also able to reduce the lipid peroxidation production and nitric oxide (NO) level, and enhance the antioxidation power in striatum from rats with HAL treatment. In order to examine the implication of NO pathway activity in HAL treatment, either NO precursor (L-arginine) or NO synthase inhibitor (L-NAME) was co‑pretreated with LT; NO precursor treatment eliminated the protective effect of LT, in contrast to that NO synthase inhibitor treatment significantly potentiated the LT effects on behavioral and biochemical protection in HAL-treated rats. These results suggested that the NO pathway was implicated, at least in part, in the HAL-induced OD, as well as in the protective effect of LT in treating HAL-induced OD. The above evidence provides a clinically relevant value for LT in delaying or treating tardive dyskinesia.

1. Chen, CN,Chang, KC,Wang, MH,Tseng, HC,Soung, HS(2018).Protective effect of L-theanine on haloperidol-induced orofacial.Chin J Physiol,61,35-41.
   連結：
2. Beers, RF, Jr,Sizer, IW(1952).A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase.J Biol Chem,195,133-140.
3. Bilska, A,Dubiel, M,Sokołowska‑Jezewicz, M,Lorenc‑Koci, E,Włodek, L(2007).Alpha‑lipoic acid differently affects the reserpine‑induced oxidative stress in the striatum and prefrontal cortex of rat brain.Neuroscience,146,1758-1771.
4. Budantsev, A,Kisliuk, OS,Shul’govskiĭ, VV,Rykunov, DS,Iarkov, AV(1993).The brain in stereotaxic coordinates (a textbook for colleges).Zh Vyssh Nerv Deiat Im I P Pavlova,43,1045-1051.
5. Burger, ME,Fachinetto, R,Zeni, G,Rocha, JB(2005).Ebselen attenuates haloperidol-induced orofacial dyskinesia and oxidative stress in rat brain.Pharmacol Biochem Behav,81,608-615.
6. Calabrese, V,Mancuso, C,Calvani, M,Rizzarelli, E,Butterfield, DA,Stella, AM(2007).Nitric oxide in the central nervous system: Neuroprotection versus neurotoxicity.Nat Rev Neurosci,8,766-775.
7. Chen, CN,Chang, KC,Lin, RF,Wang, MH,Shih, RL,Tseng, HC(2016).Nitric oxide pathway activity modulation alters the protective effects of (-) Epigallocatechin-3-gallate on reserpine-induced impairment in rats.Behav Brain Res,305,198-211.
8. Cho, CH,Lee, HJ(2013).Oxidative stress and tardive dyskinesia: Pharmacogenetic evidence.Prog Neuropsychopharmacol Biol Psychiatry,46,207-213.
9. Di, X,Yan, J,Zhao, Y,Zhang, J,Shi, Z,Chang, Y(2010).L-theanine protects the APP (Swedish mutation) transgenic SH-SY5Y cell against glutamate-induced excitotoxicity via inhibition of the NMDA receptor pathway.Neuroscience,168,778-786.
10. Ellman, GL.(1959).Tissue sulfhydryl groups.Arch Biochem Biophys,82,70-77.
11. Glazer, WM,Morgenstern, H,Schooler, N,Berkman, CS,Moore, DC(1990).Predictors of improvement in tardive dyskinesia following discontinuation of neuroleptic medication.Br J Psychiatry,157,585-592.
12. Hanff, TC,Furst, SJ,Minor, TR(2010).Biochemical and anatomical substrates of depression and sickness behavior.Isr J Psychiatry Relat Sci,47,64-71.
13. Hashimoto, M,Tanabe, Y,Fujii, Y,Kikuta, T,Shibata, H,Shido, O(2005).Chronic administration of docosahexaenoic acid ameliorates the impairment of spatial cognition learning ability in amyloid beta-infused rats.J Nutr,135,549-555.
14. Jamwal, S,Kumar, P(2017).L-theanine, a component of green tea prevents 3-nitropropionic acid (3-NP)-induced striatal toxicity by modulating nitric oxide pathway.Mol Neurobiol,54,2327-2337.
15. Kakuda, T(2011).Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction.Pharmacol Res,64,162-168.
16. Kamyar, M,Razavi, BM,Hasani, FV,Foroutanfar, A,Hosseinzadeh, H(2016).Crocin prevents haloperidol-induced orofacial dyskinesia: Possible an antioxidant mechanism.Iran J Basic Med Sci,19,1070-1079.
17. Kane, JM,Smith, JM(1982).Tardive dyskinesia: Prevalence and risk factors, 1959 to 1979.Arch Gen Psychiatry,39,473-481.
18. Kim, TI,Lee, YK,Park, SG,Choi, IS,Ban, JO,Park, HK(2009).L-theanine, an amino acid in green tea, attenuates beta-amyloid-induced cognitive dysfunction and neurotoxicity: Reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-kappaB pathways.Free Radic Biol Med,47,1601-1610.
19. Kumar, P,Kumar, A(2009).Protective effects of epigallocatechin gallate following 3-nitropropionic acid-induced brain damage: Possible nitric oxide mechanisms.Psychopharmacology,207,257-270.
20. Kumar, P,Kumar, A(2009).Effect of lycopene and epigallocatechin-3-gallate against 3-nitropropionic acid induced cognitive dysfunction and glutathione depletion in rat: A novel nitric oxide mechanism.Food Chem Toxicol,47,2522-2530.
21. Lohr, JB,Kuczenski, R,Niculescu, AB(2003).Oxidative mechanisms and tardive dyskinesia.CNS Drugs,17,47-62.
22. Misra, HP,Fridovich, I(1972).The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase.J Biol Chem,247,3170-3175.
23. Nade, VS,Kawale, LA,Yadav, AV(2010).Protective effect of Morus alba leaves on haloperidol-induced orofacial dyskinesia and oxidative stress.Pharm Biol,48,17-22.
24. Ohkawa, H,Ohishi, N,Yagi, K(1979).Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.Anal Biochem,95,351-358.
25. Patil, R,Hiray, Y,Shinde, S,Langade, P(2012).Reversal of haloperidol-induced orofacial dyskinesia by Murraya koenigii leaves in experimental animals.Pharm Biol,50,691-697.
26. Pérez-Vargas, JE,Zarco, N,Vergara, P,Shibayama, M,Segovia, J,Tsutsumi, V(2016).L-theanine prevents carbon tetrachloride-induced liver fibrosis via inhibition of nuclear factor κB and down-regulation of transforming growth factor β and connective tissue growth factor.Hum Exp Toxicol,35,135-146.
27. Raudenska, M,Gumulec, J,Babula, P,Stracina, T,Sztalmachova, M,Polanska, H(2013).Haloperidol cytotoxicity and its relation to oxidative stress.Mini Rev Med Chem,13,1993-1998.
28. Sumathi, T,Shobana, C,Thangarajeswari, M,Usha, R(2015).Protective effect of L-theanine against aluminium induced neurotoxicity in cerebral cortex, hippocampus and cerebellum of rat brain – Histopathological, and biochemical approach.Drug Chem Toxicol,38,22-31.
29. Thakur, KS,Prakash, A,Bisht, R,Bansal, PK(2015).Beneficial effect of candesartan and lisinopril against haloperidol-induced tardive dyskinesia in rat.J Renin Angiotensin Aldosterone Syst,16,917-929.
30. Thangarajan, S,Deivasigamani, A,Natarajan, SS,Krishnan, P,Mohanan, SK(2014).Neuroprotective activity of L-theanine on 3-nitropropionic acid-induced neurotoxicity in rat striatum.Int J Neurosci,124,673-684.
31. Türközü, D,Şanlier, N(2017).L‑theanine, unique amino acid of tea, and its metabolism, health effects, and safety.Crit Rev Food Sci Nutr,57,1681-1687.
32. Wang, D,Gao, Q,Wang, T,Qian, F,Wang, Y(2017).Theanine: The unique amino acid in the tea plant as an oral hepatoprotective agent.Asia Pac J Clin Nutr,26,384-391.
33. Yin, C,Gou, L,Liu, Y,Yin, X,Zhang, L,Jia, G(2011).Antidepressant-like effects of L-theanine in the forced swim and tail suspension tests in mice.Phytother Res,25,1636-1639.
34. Yoto, A,Motoki, M,Murao, S,Yokogoshi, H(2012).Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses.J Physiol Anthropol,31,28.
35. Zhang, G,Miura, Y,Yagasaki, K(2002).Effects of dietary powdered green tea and theanine on tumor growth and endogenous hyperlipidemia in hepatoma-bearing rats.Biosci Biotechnol Biochem,66,711-716.
36. Zhang, XY,Zhou, DF,Shen, YC,Zhang, PY,Zhang, WF,Liang, J(2012).Effects of risperidone and haloperidol on superoxide dismutase and nitric oxide in schizophrenia.Neuropharmacology,62,1928-1934.
37. Zheng, G,Sayama, K,Okubo, T,Juneja, LR,Oguni, I(2004).Anti-obesity effects of three major components of green tea, catechins, caffeine and theanine, in mice.In Vivo,18,55-62.
38. Zukhurova, M,Prosvirnina, M,Daineko, A,Simanenkova, A,Petrishchev, N,Sonin, D(2013).L-theanine administration results in neuroprotection and prevents glutamate receptor agonist-mediated injury in the rat model of cerebral ischemia-reperfusion.Phytother Res,27,1282-1287.