Home The impact of oxytocin on thiol/disulphide and malonyldialdehyde/glutathione homeostasis in stressed rats
Article
Licensed
Unlicensed Requires Authentication

The impact of oxytocin on thiol/disulphide and malonyldialdehyde/glutathione homeostasis in stressed rats

  • Hilal Korkmaz ORCID logo EMAIL logo , Deniz Önal , Murat Alışık , Özcan Erel and Bilge Pehlivanoğlu
Published/Copyright: July 16, 2020

Abstract

We aimed to investigate the impact of oxytocin on serum thiol/disulphide and malonylyldialdehyde (MDA)/glutathione balance under acute stress (AS) and chronic stress (CS) exposure in rats. Animals were allocated into control (C), AS and CS groups, then the groups subdivided as intranasal oxytocin or saline applied groups, randomly. Animals in the AS or CS groups were exposed to combined cold-immobilisation stress. Salivary corticosterone levels and elevated plus maze (EPM) scores were used to assess stress response. MDA, glutathione, thiol-disulphide levels were measured in the serum samples. Oxytocin treatment attenuated stress response regardless of the stress duration verified by lower corticosterone level and favorable profile in EPM parameters measured. Furthermore, oxytocin modulated oxidant profile suggesting lowered oxidant stress with decreased serum MDA/glutathione and disulfide/native thiol ratios. Oxytocin improves the response of organism to stress via both its anxiolytic and antioxidant effects. That’s why it can be considered as a protective measure to employ methods to increase endogenous oxytocin and/or to apply exogenous oxytocin to prevent stress-induced increase in oxidant stress, which plays a pivotal role in the pathogenesis of various stress-related diseases.


Corresponding author: Hilal Korkmaz, Faculty of Medicine, Department of Physiology, Gazi University, Besevler, 06510, Ankara, Turkey; Faculty of Medicine, Department of Physiology, Hacettepe University, Hacettepe, Ankara, 06230, Turkey, E-mail:

Funding source: Hacettepe University Scientific Research Projects Unit

Award Identifier / Grant number: THD2016-11895

Acknowledgments

This study was supported by Hacettepe University Scientific Research Projects Unit (No: THD2016-11895) and results are presented in 44th National Congress of Turkish Physiological Sciences Society in 2018.

  1. Author contribution: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This study was supported by Hacettepe University Scientific Research Projects Unit (No: THD2016-11895).

  3. Conflict of interest statement: The authors report no conflicts of interest.

References

Akman, T., Akman, L., Erbas, O., Terek, M.C., Taskiran, D., and Ozsaran, A. (2015). The preventive effect of oxytocin to Cisplatin-induced neurotoxicity: an experimental rat model. Biomed Res. Int. 2015: 167235, https://doi.org/10.1155/2015/167235.Search in Google Scholar

Al-Amran, F. and Shahkolahi, M. (2013). Oxytocin ameliorates the immediate myocardial injury in rat heart transplant through downregulation of neutrophil-dependent myocardial apoptosis. Transplant. Proc. 45: 2506–2512, https://doi.org/10.1016/j.transproceed.2013.03.022.Search in Google Scholar

Amin, B., Poureshagh, E., and Hosseinzadeh, H. (2016). The effect of verbascoside in neuropathic pain induced by chronic constriction injury in rats. Phytother Res. 30: 128–135, https://doi.org/10.1002/ptr.5512.Search in Google Scholar

Baker, M.A., Cerniglia, G.J., and Zaman, A. (1990). Microtiter plate assay for the measurement of glutathione and glutathione disulfide in large numbers of biological samples. Anal. Biochem. 190: 360–365, https://doi.org/10.1016/0003-2697(90)90208-q.Search in Google Scholar

Basaga, H.S. (1990). Biochemical aspects of free radicals. Biochem. Cell. Biol. 68: 989–998, https://doi.org/10.1139/o90-146.Search in Google Scholar

Birben, E., Sahiner, U.M., Sackesen, C., Erzurum, S., and Kalayci, O. (2012). Oxidative stress and antioxidant defense. World Allergy Organ. J. 5: 9–19, https://doi.org/10.1097/wox.0b013e3182439613.Search in Google Scholar

Biswas, S., Chida, A.S., and Rahman, I. (2006). Redox modifications of protein-thiols: emerging roles in cell signaling. Biochem. Pharmacol. 71: 551–564, https://doi.org/10.1016/j.bcp.2005.10.044.Search in Google Scholar

Bowman, R.E., Zrull, M.C., and Luine, V.N. (2001). Chronic restraint stress enhances radial arm maze performance in female rats. Brain Res. 904: 279–289, https://doi.org/10.1016/s0006-8993(01)02474-x.Search in Google Scholar

Busch, C.J. and Binder, C.J. (2017). Malondialdehyde epitopes as mediators of sterile inflammation. Biochim. Biophys. Acta 1862: 398–406, https://doi.org/10.1016/j.bbalip.2016.06.016.Search in Google Scholar PubMed

Coiro, V., Passeri, M., Davoli, C., Bacchi-Modena, A., Bianconi, L., Volpi, R., and Chiodera, P. (1988). Oxytocin reduces exercise-induced ACTH and cortisol rise in man. Acta Endocrinol. (Copenh.) 119: 405–412, https://doi.org/10.1530/acta.0.1190405.Search in Google Scholar PubMed

Dalle-Donne, I., Rossi, R., Giustarini, D., Milzani, A., and Colombo, R. (2003). Protein carbonyl groups as biomarkers of oxidative stress. Clin. Chim. Acta 329: 23–38, https://doi.org/10.1016/s0009-8981(03)00003-2.Search in Google Scholar

Dimsdale, J.E. (2008). Psychological stress and cardiovascular disease. J. Am. Coll. Cardiol. 51: 1237–1246, https://doi.org/10.1016/j.jacc.2007.12.024.Search in Google Scholar

Ditzen, B., Schaer, M., Gabriel, B., Bodenmann, G., Ehlert, U., and Heinrichs, M. (2009). Intranasal oxytocin increases positive communication and reduces cortisol levels during couple conflict. Biol. Psychiatr. 65: 728–731, https://doi.org/10.1016/j.biopsych.2008.10.011.Search in Google Scholar

Dos Santos, R.G., de Lima Osorio, F., Martin-Santos, R., Zuardi, A.W., Hallak, J.E.C., and Crippa, J.A.S. (2019). Modulation of the endocannabinoid and oxytocinergic systems as a potential treatment approach for social anxiety disorder. CNS Drugs 33: 1031–1038, https://doi.org/10.1007/s40263-019-00669-5.Search in Google Scholar

Erbas, O., Akman, L., Yavasoglu, A., Terek, M.C., Akman, T., and Taskiran, D. (2014). Oxytocin improves follicular reserve in a cisplatin-induced gonadotoxicity model in rats. BioMed Res. Int. 2014: 703691, https://doi.org/10.1155/2014/703691.Search in Google Scholar

Erel, O. and Neselioglu, S. (2014). A novel and automated assay for thiol/disulphide homeostasis. Clin. Biochem. 47: 326–332, https://doi.org/10.1016/j.clinbiochem.2014.09.026.Search in Google Scholar

Erkanli Senturk, G., Erkanli, K., Aydin, U., Yucel, D., Isiksacan, N., Ercan, F., and Arbak, S. (2013). The protective effect of oxytocin on ischemia/reperfusion injury in rat urinary bladder. Peptides 40: 82–88, https://doi.org/10.1016/j.peptides.2012.12.006.Search in Google Scholar

Eryilmaz, O.G., Kansu-Celik, H., Erel, O., and Erdogan, S. (2017). Thiol/disulfide parameters as a novel oxidative marker in medical labor induction with oxytocin. Horm. Mol. Biol. Clin. Invest. 29: 61–65, https://doi.org/10.1515/hmbci-2016-0032.Search in Google Scholar

Fernandez Espejo, E. (1997). Structure of the mouse behaviour on the elevated plus-maze test of anxiety. Behav. Brain Res. 86: 105–112, https://doi.org/10.1016/s0166-4328(96)02245-0.Search in Google Scholar

Gimpl, G. and Fahrenholz, F. (2001). The oxytocin receptor system: structure, function, and regulation. Physiol. Rev. 81: 629–683, https://doi.org/10.1152/physrev.2001.81.2.629.Search in Google Scholar PubMed

Glavin, G.B., Pare, W.P., Sandbak, T., Bakke, H.K., and Murison, R. (1994). Restraint stress in biomedical research: an update. Neurosci. Biobehav. Rev. 18: 223–249, https://doi.org/10.1016/0149-7634(94)90027-2.Search in Google Scholar

Gustafsson, J.E. (1978). Automated serum albumin determination by use of the immediate reaction with bromcresol green reagent. Clin. Chem. 24: 369–373, https://doi.org/10.1093/clinchem/24.2.369.Search in Google Scholar

Hong, I.S., Lee, H.Y., and Kim, H.P. (2014). Anti-oxidative effects of Rooibos tea (Aspalathus linearis) on immobilization-induced oxidative stress in rat brain. PloS One 9: e87061, https://doi.org/10.1371/journal.pone.0087061.Search in Google Scholar

Izgut-Uysal, V.N., Tan, R., Bulbul, M., and Derin, N. (2004). Effect of stress-induced lipid peroxidation on functions of rat peritoneal macrophages. Cell Biol. Int. 28: 517–521, https://doi.org/10.1016/j.cellbi.2004.04.006.Search in Google Scholar

Jafari, M., Salehi, M., Zardooz, H., and Rostamkhani, F. (2014). Response of liver antioxidant defense system to acute and chronic physical and psychological stresses in male rats. EXCLI J. 13: 161–171.Search in Google Scholar

Johnson, E.O., Kamilaris, T.C., Chrousos, G.P., and Gold, P.W. (1992). Mechanisms of stress: a dynamic overview of hormonal and behavioral homeostasis. Neurosci. Biobehav. Rev. 16: 115–130, https://doi.org/10.1016/s0149-7634(05)80175-7.Search in Google Scholar

Kanbagli, O., Balkan, J., Aykac-Toker, G., and Uysal, M. (2002). Hepatic mitochondrial prooxidant and antioxidant status in ethanol-induced liver injury in rats. Biol. Pharm. Bull. 25: 1482–1484, https://doi.org/10.1248/bpb.25.1482.Search in Google Scholar

Kant, G.J., Bunnell, B.N., Mougey, E.H., Pennington, L.L., and Meyerhoff, J.L. (1983). Effects of repeated stress on pituitary cyclic AMP, and plasma prolactin, corticosterone and growth hormone in male rats. Pharmacol. Biochem. Behav. 18: 967–971, https://doi.org/10.1016/s0091-3057(83)80022-7.Search in Google Scholar

Kara, S.S., Erel, O., Demirdag, T.B., Cura Yayla, B.C., Gulhan, B., Neselioglu, S., Polat, M., Kalkan, G., Tapisiz, A., and Tezer, H. (2016). Alteration of thiol-disulphide homeostasis in acute tonsillopharyngitis. Redox Rep. 1–5, https://doi.org/10.1080/13510002.2016.1173328.Search in Google Scholar

Katz, R.J., Roth, K.A., and Carroll, B.J. (1981). Acute and chronic stress effects on open field activity in the rat: implications for a model of depression. Neurosci. Biobehav. Rev. 5: 247–251, https://doi.org/10.1016/0149-7634(81)90005-1.Search in Google Scholar

Kent, P., Awadia, A., Zhao, L., Ensan, D., Silva, D., Cayer, C., James, J.S., Anisman, H., and Merali, Z. (2016). Effects of intranasal and peripheral oxytocin or gastrin-releasing peptide administration on social interaction and corticosterone levels in rats. Psychoneuroendocrinology 64: 123–130, https://doi.org/10.1016/j.psyneuen.2015.11.019.Search in Google Scholar PubMed

Knight, J.A., Pieper, R.K., and McClellan, L. (1988). Specificity of the thiobarbituric acid reaction: its use in studies of lipid peroxidation. Clin. Chem. 34: 2433–2438, https://doi.org/10.1093/clinchem/34.12.2433.Search in Google Scholar

Knobloch, H.S. and Grinevich, V. (2014). Evolution of oxytocin pathways in the brain of vertebrates. Front. Behav. Neurosci. 8: 31, https://doi.org/10.3389/fnbeh.2014.00031.Search in Google Scholar PubMed PubMed Central

Korkmaz, V., Kurdoglu, Z., Alisik, M., Cetin, O., Korkmaz, H., Surer, H., and Erel, O. (2016). Impairment of thiol-disulfide homeostasis in preeclampsia. J. Matern. Fetal Neonatal Med. 29: 3848–3853, https://doi.org/10.3109/14767058.2016.1149561.Search in Google Scholar PubMed

Korkmaz, V., Kurdoglu, Z., Alisik, M., Turgut, E., Sezgin, O.O., Korkmaz, H., Ergun, Y., and Erel, O. (2017). Thiol/disulfide homeostasis in postmenopausal osteoporosis. J. Endocrinol. Invest. 40: 431–435, https://doi.org/10.1007/s40618-016-0585-7.Search in Google Scholar PubMed

Lang, R.E., Heil, J.W., Ganten, D., Hermann, K., Unger, T., and Rascher, W. (1983). Oxytocin unlike vasopressin is a stress hormone in the rat. Neuroendocrinology 37: 314–316, https://doi.org/10.1159/000123566.Search in Google Scholar PubMed

Leuner, B., Caponiti, J.M., and Gould, E. (2012). Oxytocin stimulates adult neurogenesis even under conditions of stress and elevated glucocorticoids. Hippocampus 22: 861–868, https://doi.org/10.1002/hipo.20947.Search in Google Scholar PubMed PubMed Central

Mondal, T.K., Emeny, R.T., Gao, D., Ault, J.G., Kasten-Jolly, J., and Lawrence, D.A. (2015). A physical/psychological and biological stress combine to enhance endoplasmic reticulum stress. Toxicol. Appl. Pharmacol. 289: 313–322, https://doi.org/10.1016/j.taap.2015.09.013.Search in Google Scholar PubMed PubMed Central

Mostafa, T., Rashed, L.A., Osman, I., and Marawan, M. (2015). Seminal plasma oxytocin and oxidative stress levels in infertile men with varicocele. Andrologia 47: 209–213, https://doi.org/10.1111/and.12248.Search in Google Scholar PubMed

Nakhaee, A., Shahabizadeh, F., and Erfani, M. (2013). Protein and lipid oxidative damage in healthy students during and after exam stress. Physiol. Behav. 118: 118–121, https://doi.org/10.1016/j.physbeh.2013.05.028.Search in Google Scholar PubMed

Önal, D. (2016). Kronik Stres Uygulanan Sıçanlarda Oksitosinin Santral Etkisi ve Vücut Ağırlığı ile Değişimi. In: Fizyoloji Hacettepe Üniversitesi.Search in Google Scholar

Ortiz, M.S., Forti, K.M., Suarez Martinez, E.B., Munoz, L.G., Husain, K., and Muniz, W.H. (2016). Effects of antioxidant N-acetylcysteine against paraquat-induced oxidative stress in vital tissues of mice. Int. J. Sci. Basic Appl. Res. 26: 26–46.Search in Google Scholar

Pacak, K., Palkovits, M., Kvetnansky, R., Yadid, G., Kopin, I.J., and Goldstein, D.S. (1995). Effects of various stressors on in vivo norepinephrine release in the hypothalamic paraventricular nucleus and on the pituitary-adrenocortical axis. Ann. N. Y. Acad. Sci. 771: 115–130, https://doi.org/10.1111/j.1749-6632.1995.tb44675.x.Search in Google Scholar PubMed

Pacak, K., Palkovits, M., Yadid, G., Kvetnansky, R., Kopin, I.J., and Goldstein, D.S. (1998). Heterogeneous neurochemical responses to different stressors: a test of Selye’s doctrine of nonspecificity. Am. J. Physiol. 275: R1247–1255, https://doi.org/10.1152/ajpregu.1998.275.4.r1247.Search in Google Scholar

Papathanassoglou, E.D., Giannakopoulou, M., Mpouzika, M., Bozas, E., and Karabinis, A. (2010). Potential effects of stress in critical illness through the role of stress neuropeptides. Nurs. Crit. Care 15: 204–216, https://doi.org/10.1111/j.1478-5153.2010.00363.x.Search in Google Scholar

Patel, P.D., Seasholtz, A.F., and Patel, P.D. (2006). Computer-assisted scoring of the elevated plus maze. Biotechniques 41: 700–704, https://doi.org/10.2144/000112318.Search in Google Scholar

Pejic, S., Stojikjkovic, V., Todorovic, A., Gavrilovic, L., Pavlovic, I., Popovic, N., and Pajovic, S.B. (2016). Antioxidant enzymes in brain cortex of rats exposed to acute, chronic and combined stress. Folia Biol. (Krakow) 64: 189–195, https://doi.org/10.3409/fb64_3.189.Search in Google Scholar

Pellow, S., Chopin, P., File, S.E., and Briley, M. (1985). Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J. Neurosci. Methods 14: 149–167, https://doi.org/10.1016/0165-0270(85)90031-7.Search in Google Scholar

Petersson, M., Uvnas-Moberg, K., Erhardt, S., and Engberg, G. (1998). Oxytocin increases locus coeruleus alpha 2-adrenoreceptor responsiveness in rats. Neurosci. Lett. 255: 115–118, https://doi.org/10.1016/s0304-3940(98)00729-0.Search in Google Scholar

Pitman, D.L., Ottenweller, J.E., and Natelson, B.H. (1988). Plasma corticosterone levels during repeated presentation of two intensities of restraint stress: chronic stress and habituation. Physiol. Behav. 43: 47–55, https://doi.org/10.1016/0031-9384(88)90097-2.Search in Google Scholar

Putignano, P., Dubini, A., Toja, P., Invitti, C., Bonfanti, S., Redaelli, G., Zappulli, D., and Cavagnini, F. (2001). Salivary cortisol measurement in normal-weight, obese and anorexic women: comparison with plasma cortisol. Eur. J. Endocrinol. 145: 165–171, https://doi.org/10.1530/eje.0.1450165.Search in Google Scholar PubMed

Rakhshan, K., Imani, A., Faghihi, M., Nabavizadeh, F., Golnazari, M., and Karimian, S. (2015). Evaluation of chronic physical and psychological stress induction on cardiac ischemia / reperfusion injuries in isolated male rat heart: the role of sympathetic nervous system. Acta Med. Iran. 53: 482–490.Search in Google Scholar

Rammal, H., Bouayed, J., Younos, C., and Soulimani, R. (2008). Evidence that oxidative stress is linked to anxiety-related behaviour in mice. Brain Behav. Immun. 22: 1156–1159, https://doi.org/10.1016/j.bbi.2008.06.005.Search in Google Scholar PubMed

Sahin, E. and Gumuslu, S. (2007). Stress-dependent induction of protein oxidation, lipid peroxidation and anti-oxidants in peripheral tissues of rats: comparison of three stress models (immobilization, cold and immobilization-cold). Clin. Exp. Pharmacol. Physiol. 34: 425–431, https://doi.org/10.1111/j.1440-1681.2007.04584.x.Search in Google Scholar PubMed

Sanchez, M.M., Ladd, C.O., and Plotsky, P.M. (2001). Early adverse experience as a developmental risk factor for later psychopathology: evidence from rodent and primate models. Dev. Psychopathol. 13: 419–449, https://doi.org/10.1017/s0954579401003029.Search in Google Scholar

Scantamburlo, G., Ansseau, M., and Legros, J.J. (2001). Role of the neurohypophysis in psychological stress. Encephale 27: 245–259.Search in Google Scholar

Schweizer, M.C., Henniger, M.S., and Sillaber, I. (2009). Chronic mild stress (CMS) in mice: of anhedonia, ‘anomalous anxiolysis’ and activity. PloS One 4: e4326, https://doi.org/10.1371/journal.pone.0004326.Search in Google Scholar

Selye, H. (1976). Forty years of stress research: principal remaining problems and misconceptions. Can. Med. Assoc. J. 115: 53–56.Search in Google Scholar

Sesti-Costa, R., Baccan, G.C., Chedraoui-Silva, S., and Mantovani, B. (2010). Effects of acute cold stress on phagocytosis of apoptotic cells: the role of corticosterone. Neuroimmunomodulation 17: 79–87, https://doi.org/10.1159/000258690.Search in Google Scholar

Sinclair, A.J., Barnett, A.H., and Lunec, J. (1990). Free radicals and antioxidant systems in health and disease. Br J Hosp Med. 43: 334–344.Search in Google Scholar

Tas Hekimoglu, A., Toprak, G., Akkoc, H., Evliyaoglu, O., Ozekinci, S., and Kelle, I. (2013). Oxytocin ameliorates remote liver injury induced by renal ischemia-reperfusion in rats. Korean J. Physiol. Pharmacol. 17: 169–173, https://doi.org/10.4196/kjpp.2013.17.2.169.Search in Google Scholar

Tennant, C., Langeluddecke, P., and Byrne, D. (1985). The concept of stress. Aust. N. Z. J. Psychiatr. 19, 113–118, https://doi.org/10.3109/00048678509161308.Search in Google Scholar

Uvnas Moberg, K., Handlin, L., Kendall-Tackett, K., and Petersson, M. (2019). Oxytocin is a principal hormone that exerts part of its effects by active fragments. Med. Hypotheses 133: 109394, https://doi.org/10.1016/j.mehy.2019.109394.Search in Google Scholar

Wei, Y., Zhang, J.J., Li, Z., Gow, A., Chung, K.F., Hu, M., Sun, Z., Zeng, L., Zhu, T., Jia, G., (2016). Chronic exposure to air pollution particles increases the risk of obesity and metabolic syndrome: findings from a natural experiment in Beijing. Faseb J. 30: 2115–2122, https://doi.org/10.1096/fj.201500142.Search in Google Scholar

Wirth, M.M. (2015). Hormones, stress, and cognition: the effects of glucocorticoids and oxytocin on memory. Adapt. Hum. Behav. Physiol. 1: 177–201, https://doi.org/10.1007/s40750-014-0010-4.Search in Google Scholar

Wirth, M.M., Gaffey, A.E., and Martinez, B.S. (2015). Effects of intranasal oxytocin on steroid hormones in men and women. Neuropsychobiology 71: 202–211, https://doi.org/10.1159/000381023.Search in Google Scholar

Wotjak, C.T., Ganster, J., Kohl, G., Holsboer, F., Landgraf, R., and Engelmann, M. (1998). Dissociated central and peripheral release of vasopressin, but not oxytocin, in response to repeated swim stress: new insights into the secretory capacities of peptidergic neurons. Neuroscience 85: 1209–1222, https://doi.org/10.1016/s0306-4522(97)00683-0.Search in Google Scholar

Yagi, K. (1998). Simple assay for the level of total lipid peroxides in serum or plasma. Methods Mol. Biol. 108: 101–106.10.1385/0-89603-472-0:101Search in Google Scholar

Young, B.A. (1981). Cold stress as it affects animal production. J. Anim. Sci. 52: 154–163, https://doi.org/10.2527/jas1981.521154x.Search in Google Scholar PubMed

Zhu, S., Shi, R., Wang, J., Wang, J.F., and Li, X.M. (2014). Unpredictable chronic mild stress not chronic restraint stress induces depressive behaviours in mice. Neuroreport 25: 1151–1155, https://doi.org/10.1097/wnr.0000000000000243.Search in Google Scholar

Received: 2020-05-18
Accepted: 2020-06-08
Published Online: 2020-07-16
Published in Print: 2020-10-25

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 13.10.2025 from https://www.degruyterbrill.com/document/doi/10.1515/hsz-2020-0190/html
Scroll to top button