Fluoxetine and Gundelia tournefortii L. Plant Extract in Rats Exposed to Chronic Immobilization Stress; Determination of Effect on Anxiety, Motor Activity, Kidney and Liver Tissues

Abstract

This study was completed with the aim of investigating the effects of extracts obtained from Gundelia tournefortii L. and fluoxetine on anxiety, motor activity, biochemical and antioxidant parameters in rats exposed to chronic immobilization stress. The study included a total of 40 female Wistar albino rats with live weight of 200-220 g, randomly divided into groups of 8 rats with the study duration planned as 30 days. The groups created in the study were “control”, “physiologic serum + chronic immobilization”, “Gundelia tournefortii L. plant extract”, “Gundelia tournefortii L. plant extract + chronic immobilization” and “fluoxetine + chronic immobilization”. At the end of 30 days, all the groups had rotarod test (motor activity) and anxiety test (elevated plus maze) applied and after all the tests were completed the rats were sacrificed. At the end of the study, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), uric acid (UA), creatinine (CRE), total protein (TP) and albumin levels were determined. Additionally, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) activity and reduced glutathione (GSH) and malondialdehyde (MDA) levels were identified in liver and kidney tissue samples. In conclusion, administration of both Gundelia tournefortii L. plant extract and fluoxetine can be said to have positive effects on enzyme activities and MDA parameter value against experimentally-induced immobilization stress. Additionally, Gundelia tournefortii L. was not identified to have any effect on motor activity, but identified to have anxiolytic effect according to elevated plus maze test results.

Keywords

• Chronic immobilization stress
• elevated plus maze
• fluoxetine
• Gundelia tournefortii L.
• rotarod

Kronik İmmobilizasyon Stresine Maruz Bırakılan Ratlarda Fluoksetin ve Gundelia tournefortii L. Bitki Ekstresinin; Anksiyete, Motor Aktivite, Böbrek ve Karaciğer Dokuları Üzerine Etkisinin Belirlenmesi

Abstract

Bu çalışma, kronik immobilizasyon stresine maruz bırakılan ratlarda anksiyete, motor aktivite, biyokimyasal ve antioksidan parametre değerleri üzerine Gundelia tournefortii L. bitkisinden elde edilen ekstrelerin ve Fluoksetin’in etkilerinin incelenmesi amacıyla gerçekleştirilmiştir. Çalışmada canlı ağırlıkları 200-220 gr olan toplam 40 adet Wistar – albino ırkı dişi sıçan her grupta 8 sıçan olacak şekilde gruplara rastgele dağıtılmış ve çalışmanın süresi toplam 30 gün olarak planlanmıştır. Çalışmadaki gruplar; “Kontrol”, “Serum fizyolojik su + Kronik İmmobilizasyon”, “Gundelia tournefortii L. bitki ekstresi”, “Gundelia tournefortii L. bitki ektresi + Kronik immobilizasyon” ve “Fluoksetin + Kronik immobilizasyon stresi” şeklinde oluşturulmuştur. 30’uncu gün sonunda tüm gruplara rotarod testi (motor aktivite testi) ve anksiyete testi (yükseltilmiş artı labirent testi) uygulananarak tüm testler tamamlandıktan sonra uygulama sonunda sıçanlar sakrifiye edilmiştir. Çalışma sonunda aspartat aminotransferaz (AST), alanin aminotransferaz (ALT), alkalen fosfataz (ALP), ürik asit(UA), kreatinin (CRE), total protein (TP), albumin düzeyleri belirlenmiştir. Ayrıca, karaciğer ve böbrek dokusu örneklerinde katalaz (CAT), süperoksid dismutaz (SOD), glutatyon peroksidaz (GPx), glutatyon S-transferaz (GST), glutatyon redüktaz (GR) aktiviteleri ve redükte glutatyon (GSH) ile malondialdehit (MDA) düzeyleri tespit edilmiştir. Sonuç olarak, deneysel olarak oluşturulan immobilizasyon stresine karşı, hem Gundelia tournefortii L. bitki ekstresinin hem de Fluoksetin uygulamasının enzim aktiviteleri üzerine ve MDA parametre değeri üzerine olumlu etkiler sergilediği söylenebilir. Bununla birlikte, Gundelia tournefortii L. bitkisinin; motor aktivite üzerine herhangi bir etkisi olmadığı tespit edilirken, yükseltilmiş artı labirent testi sonuçlarına göre, anksiyolitik etkisi olduğu belirlenmiştir.

Keywords

• Fluoksetin, Gundelia tournefortii L.
• kronik immobilizasyon stresi
• rotarod
• yükseltilmiş artı labirent

References

1. Aebi H. Catalase. In: Bergemeyer HU (ed) Methods of Enzymatic Analysis. Academic. Press, New York-London. 1974; 673-84.
2. Ali SN, Ahmad MK, Mahmood R. Sodium chlorate, a herbicide and major water disinfectant byproduct, generates reactive oxygen species and induces oxidative damage in human erythrocytes. Environ Sci Pollut Res Int 2017; 24(2):1898-909.
3. APPI. Amercan Psychiatric Pub Incorporated Diagnostic and statistical manual of mental disorders:DSM-V.[https://psychiatryonline.org/pbassets/dsm/update/. Data of access: 01.01.2018.
4. Asadi-samani M, Rafieian-Kopaei M, Azimi N. Gundelia: a systematic review of medicinal and molecular perspective. Pak J Biol Sci 2013; 16(21):1238-47.
5. Asgary S, Movahedian A, Badiei A, Naderi Amini GF, Hamidzadeh Z. Effect of Gundelia tournefortii on some cardiovascular risk factors in animal model. J Med Plants 2009; 7: 112-9.
6. Aykac A, Suer K, Taskiran C. Models of rat behavior used for studies of anxiety. Marmara Medical Journal 2015; 28(1): 1-7.
7. Azeez OH, Kheder AE. Effect of Gundelia tournefortii on some biochemical parameters in dexamethasone-induced hyperglycemic and hyperlipidemic mice. Iraqi J Vet Sci 2012; 26: 73-9.
8. Bandyopadhyay U, Das D, Banerjee RK. Reactive oxygen species: oxidative damage and pathogenesis. Current Sci 1999; 658-66.

9. Barbieri A, Palma G, Rosati A, Giudice A, Falco A, Petrillo A, Bimonte S, Benedetto M, Esposito G, Stiuso P, Abbruzzese A, Caraglia M, Arra C. Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted tumour growth. J Cell Mol Med 2012; 16(4):920-6.
10. Barnett SA. The rat: a study in behavior. New Jersey: Transaction Publishers. 2007.
11. Belzung C, Le Guisquet AM, Barreau S, Calatayud F. An investigation of the mechanisms responsible for acute fluoxetine induced anxiogenic-like effects in mice. Behav Pharmacol 2001; 12: 151-62.
12. Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963; 61(5):882-8.
13. Borges RL, Ribeiro AB, Zanella MT, Batista MC. Uric acid as a factor in the metabolic syndrome. Curr Hypertens Rep 2010; 12: 113-9.
14. Borsini F, Podhorna J, Marazziti D. Do animal models of anxiety predict anxiolytic-like effects of antidepressants. Psychopharmacology 2002; 163:121-41.
15. Buyukdereli Z. To evaluate the effect of thrombocyte stimulating factor antagonist application on cognitive and motor abilities in newborn rats with hypoxic ischemic brain injury. Thesis, Mersin University Faculty of Medicine, Department of Pediatrics, Mersin, Turkey. 2008.
16. Carlberg I, Mannervik B. Glutathione reductase. Methods Enzymol 1985; 113:484-90.
17. Coleta M, Batista MT, Campos MG, Carvalho R, Cotrim MD, Lima TC, Cunha AP. Neuropharmacologi calevaluation of the putative anxiolytic effects of Passi floraedulis Sims, its sub-fractions and flavonoid constituents. Phytother Res 2006; 20(12):1067-73.
18. Coruh N, Celep AS, Ozgokce F, Iscan M. Antioxidant capacities of Gundelia tournefortii L. extracts and inhibition on glutathione-S-transferase activity. Food Chem 2007; 100(3):1249-53.
19. Crawley J, Goodwin FK. Preliminary report of a simple animal behaviour forthe anxiolytic effects of benzodiazepines. Pharmacol Biochem Behav 1980; 13: 167-70.
20. Davydov VV, Zakharchenko IV, Ovsyannikov VG. Free radical processes in the liver of adult and old rats during stress. Bull Exp Biol Med 2004; 137: 139-42.
21. Dias PM, Changarath J, Damodaran A, Joshi MK. Compositional variation among black tea across geographies and their potential influence on endothelial nitric oxide and antioxidant activity. J Agric Food Chem 2014; 62: 6655-68.
22. Djordjevic J, Djordjevic A, Adzic M, Niciforovic A, Radojcic MB. Chronic stress differentially affects antioxidant enzymes and modifies the acute stress response in liver of Wistar rats. Physiol Res 2010; 59(5): 729-36.
23. Dong K, Wu M, Liu X, Huang Y, Zhang D, Wang Y, Yan LJ, Shi D. Glutaredoxins concomitant with optimal ROS activate AMPK through S-glutathionylation to improve glucose metabolism in type 2 diabetes. Free Radic Biol Med 2016; 101: 334-47.
24. Doukkalil Z, Kamal R, Jemeli ME, Nadjmouddine M, Zellou A, Cherrah Y, Alaoui K, Taghzouti K. Anti-Anxiety Effects of Mercurialis 608 Annua Aqueous Extract in the Elevated Plus Maze Test. Pharmaceutical Bioprocessing 2016; 609(4): 52-7.
25. Eddouks M, Maghrani M, Zeggwagh NA, Michel JB. Study of the hypoglycaemic activity of Lepidium sativum L. aqueous extract in normal and diabetic rats. J Ethnopharmacology 2005; 97: 391-5. El S, Salem E, Abdel R. In vitro hepatotoxicity of alachlor and its by-product. J Appl Toxicol 2002; 22: 31-5.
26. Erdem E, Ozdemir A, Kaya C, Karatas A, Cengiz K. Serum Uric Acid Levels in Chronic Kidney Disease. Fırat Medicine Journal 2012; 17(1): 23-7.
27. Ferrante RJ, Andreassen OA, Dedeoglu A, Ferrante KL, Jenkins BG, Hersch SM, Beal MF. Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease. J Neurosci 2002; 22(5): 1592-9.
28. Gokcimen A, Gulle K, Demirin H, Bayram D, Kocak A, Altuntas I. Effects of DZN at different doses on rat liver and pancreas tissues. Pest Biochem Physiol 2007; 87: 103-8.
29. Gulati K, Chakraborti A, Ray A. Differential role of nitric oxide (NO) in acute and chronic stress induced neurobehavioral modulation and oxidative injury in rats. Pharmacol Biochem Behav 2009; 92(2): 272-6.
30. Gutteridge JMC. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 1995; 41: 1819-28.
31. Haghi G, Hatami A, Arshi R. Distribution of caffeic acid derivatives in Gundelia tournefortii L. Food Chem 2011; 124: 1029-35.
32. Halabi S, Battah AA, Aburjai T, Hudaib M. Phytochemical and antiplatelet investigation of Gundelia tournefortii. Pharm Biol 2005; 43: 496-500.
33. Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine, 3rd ed, Oxford University Pres, New York. 1999; 246-351.
34. Hamdan LL, Afifi FU. Studies on the in vitro and in vivo hypoglycemic activities of some medicinal plants used in treatment of diabetes in Jordanian traditional medicine. J Ethnopharmacol 2004; 93(1):117-21. Hammadi SK, Salam AJ. Hypolipemic effect of Kuub (Gundelia tournefortii A.) oil and clofibrate on lipid profile of atherosclerotic rats. Veterinarski Arhiv 2004; 74: 359-69.
35. Jain SK, McVie R, Duett J, Herbst JJ. Erythrocyte membrane lipid peroxidation and glycosylated hemoglobin in diabetes. Diabetes 1989; 38: 1539-43.
36. Jamshidzadeh A, Fereidooni F, Salehi Z, Niknahad H. Hepatoprotective activity of Gundelia tourenfortii. J Ethnopharmacol 2005; 101:233-7.
37. Jones DP, Kennedy FG. Function of glutathione peroxidase in decomposition of hydrogen peroxide in isolated liver and heart cells. In Fanctions of Glatathione: Biochemical, Physiological, Toxicological and Clinical dspects In: Larsson A, Orrenius S, Holmgren A, Mannervik B, (Eds.), Functions of Glutathione. Raven Press, New York. 1983; 109-16.
38. Kaur C, Ling EA. Blood brain barrier in hypoxic-ischemic conditions. Current Neurovascular Res 2008; 5(1): 71-81.
39. Kessler RC, Sonnega A. Posttraumatic stress disorder in the national comorbidity survey. Arch Gen Psychiatry 1995; 52: 1048-60.
40. Kovacheva-Ivanova S, Bakalova R, Ribavov SR. Immobilization stress enhances lipid peroxidation in the rat lungs. Gen Physiol Biophys 1994; 13: 469-82.
41. Kurt M, Celik S, Kesim Y. The Role of dopaminergic system in motor coordination. Journal of Experimental and Clinical Medicine 2002; 19(1):15-24.
42. Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: impact on human health. Pharmacogn Rev 2010; 4: 118-26.
43. Mannervik B, Guthenberg C. Glutathione S-transferase (Human Plasenta). Methods Enzymol 1981; 77: 231-5.
44. Marder M, Paladini AC. GABA (A)-receptorligands of flavonoid structure. Current Topics in Med Chem 2002; 2: 853-67.
45. Matthäus B, Ozcan MM. Chemical evaluation of flower bud and oils of tumbleweed (Gundelia tournefortii L.) as a new potential nutrition sources. J Food Biochem 2011; 35: 1257-66.
46. Nakatani N, Kayano S, Kikuzaki H, Sumino K, Katagiri K, Mitani T. Identification, quantitative determination, and antioxidative activities of chlorogenic acid isomers in prune (Prunus domestica L.). J Agric Food Chem 2000; 48: 5512-6.
47. Oishi K, Yokoi M, Maekawa S, Sodeyama C, Shiraishi T, Kondo R, Kuriyama T, Machida K. Oxidative stress and haematological changes in immobilized rats. Acta Physiol Scand 1999; 165: 65-9.
48. Oryan S, Nasri S, Amin G, Kazemi-Mohammady M. Anti nociceptive and anti-inflammatory effects of aerial parts of Gundelia tournefortii L. on NMRI male mice. J Shahrekord Univ Med Sci 2011; 12: 8-15.
49. Pedreanez A, Arcaya JL, Carrizo E. Experimental depression induces renal oxidative stress in rats. Physiol Behav 2011; 104(5):1002-9.
50. R Core Team: A language and environment for statistical computing, R Foundation for Statistical Computing, Vienna, Austria, 2018.
51. Salim S, Asghar M, Taneja M, Hovatta I, Chugh G, Vollert C, Vu A. Potential contribution of oxidative stress and inflammation to anxiety and hypertension. Brain Res 2011; 1404: 63-71.
52. Samarghandian S, Azimi-Nezhad M, Farkhondeh T, Samini F. Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney. Biomedicine & Pharmacotherapy 2017; 87: 223-9.
53. Soliman KM, Abdul-Hamid M, Othman AI. Effect of carnosine on gentamicin-induced nephrotoxicity. Med Sci Monit 2007; 13: 73-83.
54. Starevic V, Linden M, Uhlenhuth EH, Kolar D, Latas M. Treatment of panic disorder with agoraphobia in an anxiety disorders clinic: factors influencing psychiatrists’ treatment choice. Psychiatry Res 2004; 125: 41-52.
55. Sahin E, Gumuslu S. Immobilization stress in rat tissues: alterations in protein oxidation, lipid peroxidation and antioxidant defense system. Comparative Biochemistry and Physiology Part C: Toxicology and Pharmacology 2007;144(4):342-7.
56. Turan A, Celik I. Antioxidant and hepatoprotective properties of dried fig against oxidative stress and hepatotoxicity in rats. Int J of Biol Macromol 2016; 91: 554-9.
57. Valko M, Leibfritz D, Moncol J, Cronin M, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39: 44-84.
58. Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxietyrelated behavior in rodents. Nat Protoc 2007; 2(2): 322-8.
59. Yang L, Wang M, Guo YY, Sun T, Li YJ, Yang Q, Zhang K, Liu SB, Wu YM. Systemic inflammation induces anxiety disorder through CXCL12/CXCR4 pathway. Brain Behav Immun 2016; 56: 352-62.
60. Yuan Y, Wu SJ, Liu X, Zhang LL. Antioxidant effect of salidroside and its protective effect against furan-induced hepatocyte damage in mice. Food Funct 2013; 4(5):763-9.
61. Yurt B, Celik I. Hepatoprotective effect and antioxidant role of sun, sulphited-dried apricot (Prunus armeniaca L.) and its kernel against ethanol-induced oxidative stress in rats. Food and Chem Toxicology 2011; 49(2): 508-13.
62. Zafir A, Banu N. Antioxidant potential of fluoxetine in comparison to Curcuma longa in restraint -stressed rats. Eur J of Pharmacology 2007; 572: 23-31.
63. Zaidi SM, Al-Qirim TM, Banu N. Effects of antioxidant vitamins on glutathione depletion and lipid peroxidation induced by restraint stress in the rat liver. Drugs R&D 2005; 6: 157-65.