Investigations on Tissue Lipid Peroxidation, Glutathione and Antioxidant Enzyme Levels in the Hippocampus of Adult Rats in Experimental Hypo- and Hyperthyroidism Induced by Propyl Thiouracil (PTU) and L-Thyoxine

Year 2022, Volume: 11 Issue: Supplement 1 - Veterinary Pharmacology Congress Special Issue, 22 - 28, 01.12.2022

Bilal Cem Liman Narin Liman Yasin Tekeli Ergül Ergen Ural Kemal Kavraal

https://doi.org/10.53424/balikesirsbd.1149397

Abstract

Objective: This study aimed to explore the effect of experimental hypo- and hyperthyroidism on the lipid peroxidation and glutathione levels, and the activities of antioxidant system in the rat hippocampus. Material and Methods: The study included 72 adult male Wistar albino rats which were grouped as follows: (1) control group (2) hypothyroidism group: induced by intraperitoneal injection of 10 mg/kg/day propylthiouracil (PTU) for 4 weeks; (3) hyperthyroidism group: induced by 4-week thyroxine injection (0.3 mg/kg/day). The levels of lipid peroxidation, glutathione (GSH), antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in the hippocampus of rats with hypo- and hyperthyroidism were examined using ELISA techniques. Conclusion: It can be said that TH disorder may affect cognitive performance by causing some changes in the antioxidant defense system of the hippocampus.

Keywords

Hypothyroidism, Hyperthyroidism, propylthiouracyl, L-thyroxine, Hippocampus, Antioxidant enzyme systems

Supporting Institution

ERÜ BAP

Project Number

TCD-2017-7642

Propil Tiyourasil (PTU) ve L-Tiroksin ile Oluşturulan Deneysel Hipo- ve Hipertiroidizm Erişkin Sıçanların Hipokampüsünde Doku Lipid Peroksidasyonu, Glutatiyon ve Antioksidan Enzim Düzeyleri Üzerine Araştırmalar

Abstract

Amaç: Bu çalışmanın amacı deneysel hipo- ve hipertiroidizm oluşturulan sıçan modelinde hipokampüsde lipid peroksidasyon ve düzeyleri ile antioksidan enzim aktivitelerinin değişip değişmediğini ortaya koymaktır. Materyal ve Metod: Çalışmada kullanılan 72 yetişkin erkek Wistar albino sıçan aşağıdaki şekilde gruplandırıldı: (1) kontrol grubu (2) hipotiroidizm grubu: 4 hafta boyunca 10 mg/kg/gün propiltiourasil (PTU)’in intraperitoneal enjeksiyonu ile indüklendi; (3) hipertiroidizm grubu: 4 haftalık tiroksin enjeksiyonu (0.3 mg/kg/gün) ile indüklendi. Hipo ve hipertirodi oluşturulan sıçanların hipokampüslerinde lipid peroksidasyon düzeyleri, glutatyon (GSH) düzeyi, antioksidan enzimlerden süperoksit dismutaz (SOD), katalaz (CAT), glutatyon peroksidaz (GPx) ve glutatyon redüktaz (GR) düzeyleri ELISA ile incelendi. Bulgular: Çalışmamızın ELISA analiz sonuçları hipo- ve hipertiroidizmin hipokampal lipid peroksidasyonunu etkilemediğini, ancak hipotiroidi oluşturulan sıçanların hipokampüs örneklerinde SOD düzeylerinin kontrol grubuna göre anlamlı olarak düşük olduğunu (P<0.05) ve hipokampüsde antioksidan enzimlerin düzeylerinin değişmediğini gösterdi. Sonuç: Tiroid hormon (TH) bozukluğunun hipokampüsün antioksidan savunma sisteminde bazı değişikliklere neden olabileceği söylenebilir.

Keywords

Hipotiroidizm, Hipertiroidizm, propiltiyourasil, L-tiroksin, Hipokampüs, Antioksidan enzim sistemler

Project Number

TCD-2017-7642

References

• Brent, G.A. (2011). Mechanisms of thyroid hormone action. Journal of Clinical Investigation 122: 3035–3043. https://doi.org/10.1172/JCI60047.
• Cano-Europa, E., Pérez-Severiano, F., Vergara, P., Ortiz-Butrón, R., Ríos, C., Segovia, J., Pacheco-Rosado, J. (2008). Hypothyroidism induces selective oxidative stress in amygdala and hippocampus of rat. Metabolic Brain Disease 23: 275–287. https://doi.org/10.1007/s11011-008-9099-0.
• Charles, H.E. (2018). Hypothyroidism can be given between meals with similar effectiveness at various times of the day. Clinical Thyroidology 30: 456–459. https://doi.org/10.1089/ct.2018;30.456-459
• Dobrzynska, M.M., Baumgartner, A., Anderson, D. (2004). Antioxidants modulate thyroid hormone- andnoradrenaline-induced DNA damage in human sperm. Mutagenesis 19: 325–330. https://doi.org/10.1093/mutage/geh037
• Dringen, R., Gutterer, J.M., Hirrlinger, J. (2000). Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. European Journal of Biochemistry 267: 4912–4916. https://doi.org/10.1046/j.1432-1327.2000.01597.x
• Dwivedi, D., Megha, K., Mishra, R., Mandal, P.K. (2020). Glutathione in Brain: Overview of its conformations, functions, biochemical characteristics, quantitation and potential therapeutic role in brain disorders. Neurochemical Research 45: 1461–1480.
• Elkalawy, S., Abo-Elnour, R., El, D.D., Yousry, M. (2013). Histological and immunohistochemical study of the effect of experimentally induced hypothyroidism on the thyroid gland and bone of male albino rats. Egypt J Histology 36: 92–102. https://doi.org/10.1097/01.EHX.0000424169.63765.ac
• Fukai, T., Ushio-Fukai, M. (2011). Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxidans and Redox Signaling 15: 1583–1606. https://doi.org/10.1089/ars.2011.3999
• Guo, Y., Wan, S., Zhong, X., Zhong, M.K., Pan, T.R. (2014). Levothyroxine replacement therapy with vitamin E supplementation prevents the oxidative stress and apoptosis in hippocampus of hypothyroid rats. Neuroendocrinology Letters 35: 684–690
• Hang, X.W., Yang, R.I., Zhao, Z.Y., Ji, C., Yang. (2005) Mechanism for apoptosis of hippocampus neuron induced by hypothyroidism in perinatal rats. Journal of Zhejiang University, Medical sciences 34: 298–303. https://doi.org/10.3785/j.issn.1008-9292.2005.04.003
• Hidayat, M., Khaliq, S., Khurram, A., Lone, K. (2019). Protective effects of melatonin on mitochondrial injury and neonatal neuron apoptosis induced by maternal hypothyroidism. Melatonin Research, 2: 42–60. https://doi.org/10.32794/mr11250040
• Hwang, J.H., Kang, S.Y., Kang, A.N., Jung, H.W., Jung, C., Jeong, J.H., Park, Y.K. (2017). MOK, a pharmacopuncture medicine, regulates thyroid dysfunction in L-thyroxin-induced hyperthyroidism in rats through the regulation of oxidation and the TRPV1 ion channel. BMC Complement Alternative Medicine, 17: 535. https://doi.org/10.1186/s12906-017-2036-1
• Karbownik-Lewińska, M., Kokoszko-Bilska, A. (2012). Oxidative damage to macromolecules in the thyroid– experimental evidence. Thyroid Research, 5: 25. https://doi.org/10.1186/1756-6614-5-25
• Leto, T.L., Morand S., Hurt, D., Ueyama, T. (2009). Targeting and regulation of reactive oxygen species generation by Noxfamily NADPH oxidases. Antioxidans and Redox Signaling, 11: 2607– 2619.
• Marnett, L.J. (1999). Lipid peroxidation-DNA damage by malondialdehyde. Mutation Research, 424: 83–95.
• Mates, J.M., Perez-Gomez, C., Castro, I.N. (1999). Antioxidant enzymes and human diseases. Clinical Biochemistry 32: 595–603 https://doi.org/10.1016/S0009-9120(99)00075-2
• Mogulkoç, R., Baltacı, A.K., Öztekin, E., Aydın, L., Sivrikaya, A. (2006). Melatonin prevents oxidant damage in various tissues of rats with hyperthyroidism. Life Science, 79: 311–315. https://doi.org/10.1016/j.lfs.2006.01.009
• Niki, E., Yoshida, Y., Saito, Y., Noguchi, N. (2005). Lipid peroxidation: mechanisms, inhibition, and biological effects. Biochemical and Biophysical Research Communications, 338: 668–376. https://doi.org/10.1016/j.bbrc.2005.08.072
• Oktay, S, Uslu L, Emekli N. (2017). Effects of altered thyroid states on oxidative stress parameters in rats. Journal of Basic and Clinical Physiology and Pharmacology, 28: 159–165.
• Pan, T.R., Zhong, M.K., Zhong, X., Zhang, Y.Q., Zhu, D. (2012). Levothyroxine replacement therapy with vitamin E supplementation prevents oxidative stress and cognitive deficit in experimental hypothyroidism. Endocrine, 43:434–439. https://doi.org/10.1007/s12020-012-9801-1
• Radi, R., Turrens, J.F., Chang, L.Y., Bush, K.M., Crapo, J.D., Freeman, B.A. (1991). Detection of catalase in rat heart mitochondria. Journal of Biological Chemistry, 266: 22028–22034.
• Rigutto, S., Hoste, C., Grasberger, H., Milenkovic, M., Communi, D., Dumont, J.E., Corvilain, B., Miot, F., De Deken, X. (2009). Activation of dual oxidases Duox1 and Duox2: differential regulation mediated by camp-dependent protein kinase and protein kinase C-dependent phosphorylation. Journal of Biological Chemistry, 284: 6725–6734.
• Sinet, P.M. and Ceballos-Picot, I. (1992). Free Radicals in the Brain. Springer Verlag, Berlin, pp 91–98.
• Soukup, T., Zacharová, G., Smerdu, V., Jirmanová I. (2001). Body, heart, thyroid gland and skeletal muscle weight changes in rats with altered thyroid status. Physiological Research, 50: 619–626.
• Trevisan, M., Browne, R., Ram, M., Muti, P., Freudenheim J., Carosella, A.M., Armstrong, D. (2001). Correlates of markers of oxidative status in the general population. American Journal of Epidemiology 154: 348–356.
• Venditti, P., Balestrieri, M., Di Meo, S., De Leo, T. (1997). Effect of thyroid state on lipid peroxidation, antioxidantdefences, and susceptibility to oxidative stress in rat tissues. Journal of Endocrinology, 155: 151–157.
• Yilmaz, S., Ozan, S., Benzer, F., Canatan, H. (2003). Oxidative damage and antioxidant enzyme activities inexperimental hypothyroidism. Cell Biochemistry & Function, 21: 325–330. https://doi.org/10.1002/cbf.1031
• Wu, G., Fang Y.Z., Yang, S., Lupton, J.R., Turner, N.D. (2004). Glutathione metabolism and its implications for health. Journal of Nutrition, 134: 489–492. https://doi.org/10.1093/jn/134.3.489
• Yang, J., Yi, N., Zhang J., et al. (2018). Generation and characterization of a hypothyroidism rat model with truncated thyroid stimulating hormone receptor. Scientific Report, 8: 4004. https://doi.org/10.1038/s41598-018-22405-7
• Zhu, Y., Carvey, P.M., Ling, Z. (2006). Age-related changes in glutathione and glutathione related enzymes in rat brain. Brain Research, 1090: 35–44. https://doi.org/10.1016/j.brainres.2006.03.063