Abstract
Previous studies have shown sex-specific oxidative changes in spinal cord of rats submitted to chronic stress, which may be due to gonadal hormones. Here, we assessed total radical-trapping potential (TRAP), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and lipid peroxidation (evaluated by the TBARS test) in the spinal cord of ovariectomized (OVX) female rats. Female rats were subjected to OVX, and half of the animals received estradiol replacement. Animals were subdivided into controls and chronically stressed (for 40 days). Our findings demonstrate that chronic stress decreased TRAP, and increased SOD activity in spinal cord homogenates from ovariectomized female rats and had no effect on GPx activity. On the other hand, groups receiving 17β-estradiol replacement presented a decreased GPx activity, but no alteration in TRAP and in SOD activity. No differences in the TBARS test were found in any of the groups analyzed. In conclusion, our results support the idea that chronic stress induces an imbalance between SOD and GPx activities, additionally decreasing TRAP. Estradiol replacement did not reverse the effects of chronic stress, but induced a decrease in GPx activity. Therefore, estradiol replacement in ovariectomized chronically stressed rats could make the spinal cord more susceptible to oxidative injury.
Similar content being viewed by others
References
Halliwell B, Gutteridge JMC (2007) Free radicals in biology and medicine, 4th edn. Oxford University Press, Oxford
Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97(6):1634–1658
Madrigal JL, Garcia-Bueno B, Caso JR et al (2006) Stress-induced oxidative changes in brain. CNS Neurol Disord Drug Targets 5(5):561–568
Bardakci H, Kaplan S, Karadeniz U et al (2006) Methylene blue decreases ischemia-reperfusion (I/R)-induced spinal cord injury: an in vivo study in an I/R rabbit model. Eur Surg Res 38(5):482–488
Tabajara AS, Fontella FU, Torres ILS et al (2003) Gender differences in oxidative stress in spinal cord of rats submitted to repeated restraint stress. Neurochem Res 28(9):1315–1320
Sorrells SF, Caso JR, Munhoz CD et al (2009) The stressed CNS: when glucocorticoids aggravate inflammation. Neuron 64(1):33–39
Ceccatelli S, Tamm C, Zhang Q et al (2007) Mechanisms and modulation of neural cell damage induced by oxidative stress. Physiol Behav 92(1–2):87–92
Prediger ME, Gamaro GD, Crema LM et al (2004) Estradiol protects against oxidative stress induced by chronic variate stress. Neurochem Res 29(10):1923–1930
Fontella FU, Bruno AN, Balk RS et al (2005) Repeated stress effects on nociception and on ectonucleotidase activities in spinal cord synaptosomes of female rats. Physiol Behav 2:213–219
de Vasconcellos AP, Nieto FB, Crema LM (2006) Chronic lithium treatment has antioxidant properties but does not prevent oxidative damage induced by chronic variate stress. Neurochem Res 31(9):1141–1151
Zafir A, Banu N (2009) Modulation of in vivo oxidative status by exogenous corticosterone and restraint stress in rats. Stress 12(2):167–177
Torres ILS, Buffon A, Silveira PP et al (2002) Effect of chronic and acute stress on ecto-nucleotidase activities in spinal cord. Physiol Behav 75:1–5
Gamaro GD, Xavier MH, Denardin JD et al (1998) The effects of acute and repeated restraint stress on the nociceptive response in rats. Physiol Behav 63:693–697
Crema LM, Vendite D, Horn AP et al (2009) Effects of chronic restraint stress and estradiol replacement on glutamate release and uptake in the spinal cord from ovariectomized female rats. Neurochem Res 34(3):499–507
Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1–105
Torres IL, Vasconcellos AP, Silveira SN et al (2001) Effect of repeated stress on novelty-induced antinociception in rats. Braz J Med Biol Res 34:241–244
Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275
Lissi E, Pascual C, Del Castillo MD (1992) Luminol luminescence induced by 2, 2′-Azo-bis(2-amidinopropane) thermolysis. Free Radic Res Commun 17:299–311
Evelson P, Travacio M, Repetto M et al (2001) Evaluation of total reactive antioxidant potential (TRAP) of tissue homogenates and their cytosols. Arch Biochem Biophys 388:261–266
Lissi E, Salim-Hanna M, Pascual C et al (1995) Evaluation of total antioxidant potential (TRAP) and total antioxidant reactivity from luminol-enhanced chemiluminescence measurements. Free Radic Biol Med 18(2):153–158
Delmas-Beauvieux MC, Peuchant E, Dumon MF et al (1995) Relationship between red blood cell antioxidant enzymatic system status and lipid peroxidation during the acute phase of malaria. Clin Biochem 28:163–169
Wendel A (1981) Glutathione peroxidase. Methods Enzymol 77:325–333
Buege JA, Aust SD (1978) Microssomal lipid peroxidation. Methods Enzymol 52:302–310
Yagi K (1998) Simple for the level of total lipid peroxides in serum or plasma. In: Armstrong D (ed) Free radical and antioxidant protocols, 108. Humana Press Inc, Totowa, pp 101–106
Llesuy S, Evelson P, Gonzalez Flecha B et al (1994) Oxidative stress in muscle and liver of rats with septic syndrome. Free Radic Biol Med 16:445–451
Behl C, Skutella T, Lezoualch F et al (1997) Neuroprotection against oxidative stress by estrogens: structure–activity relationship. Mol Pharmacol 51:535–541
Manoli LP, Gamaro GD, Silveira PP et al (2000) Effect of chronic variate stress on thiobarbituric-acid reactive species and on total radical-trapping potential in distinct regions of rat brain. Neurochem Res 25(7):915–921
Afonso V, Champy R, Mitrovic D et al (2007) Reactive oxygen species and superoxide dismutases: role in joint diseases. Joint Bone Spine 74(4):324–329
Kaynar MY, Hanci M, Kuday C et al (1994) Changes in the activity of antioxidant enzymes (SOD, GPX, CAT) after experimental spinal cord injury. Tokushima J Exp Med 41(3–4):133–136
Noschang CG, Krolow R, Pettenuzzo LF et al (2009) Interactions between chronic stress and chronic consumption of caffeine on the enzymatic antioxidant system. Neurochem Res 34(9):1568–1574
Pajović SB, Saicić ZS (2008) Modulation of antioxidant enzyme activities by sexual steroid hormones. Physiol Res 57(6):801–811
McIntosh LJ, Hong KE, Sapolsky RM (1998) Glucocorticoids may alter antioxidant enzyme capacity in the brain: baseline studies. Brain Res 791(1–2):209–214
Chen JX, Tang YT, Yang JX (2008) Changes of glucocorticoid receptor and levels of CRF mRNA, POMC mRNA in brain of chronic immobilization stress rats. Cell Mol Neurobiol 28(2):237–244
Chong ZZ, Faqi L, Maiese K (2005) Oxidative stress in the brain: novel cellular targets that govern survival during neurodegenerative disease. Prog Neurobiol 75:207–246
Fisher AB, Dodia C, Manevich Y et al (1999) Phospholipid hydroperoxides are substrates for non-selenium glutathione peroxidase. J Biol Chem 274:21326–21334
Howard SA, Hawkes WC (1998) The relative effectiveness of human plasma glutathione peroxidase as a catalyst for the reduction of hydroperoxides by glutathione. Biol Trace Elem Res 6:127–136
Behl C, Holsboer F (1999) The female sex hormone oestrogen as a neuroprotectant. Trends Pharmacol Sci 20:441–444
Brinton RD, Chen S, Montoya M et al (2000) The women’s health initiative estrogen replacement therapy is neurotrophic and neuroprotective. Neurobiol Aging 21:475–496
Singh M, Setalo G Jr, Guan X et al (1999) Estrogen-induced activation of mitogen-activated protein kinase in cerebral cortical explants: convergence of estrogen and neurotrophin signaling pathways. J Neurosci 19:1179–1188
Nilsen J, Chen S, Brinton RD (2002) Dual action of estrogen on glutamate-induced calcium signaling: mechanisms requiring interaction between estrogen receptors and src/mitogen activated protein kinase pathway. Brain Res 930:216–234
Stambolic V, Woodgett JR (1994) Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation. Biochem J 303:701–704
Coghlan MP, Culbert AA, Cross DA et al (2000) Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem Biol 7:793–803
Schmidt AJ, Krieg JC, Vedder H (2002) Estradiol increased GSH levels in hippocampal, neocortical and C6 cell culture. J Neurosci Res 67(4):544–550
Ozacmak VH, Sayan H (2009) 17β-estradiol administration ameliorated ischemia-induced decrease in GSH levels in hippocampus and cortex cerebral from old rats. Physiol Res 58(6):909–912
Konyalioglu S, Durmaz G, Yalcin A (2007) The potential antioxidant effect of raloxifene treatment: a study on heart, liver and brain cortex of ovariectomized female rats. Cell Biochem Funct 25(3):259–266
Feng Z, Zhang JT (2005) Brain mitochondrial GSH levels were severely depleted in the brain of OVX. Free Radic Biol Med 39(2):195–204
Łukaszewicz-Hussain A, Moniuszko-Jakoniuk J (2003) Liver catalase, glutathione peroxidase and reductase activity, reduced glutathione and hydrogen peroxide levels in acute intoxication with chlorfenvinphos, an organophosphate insecticide. Polish J Environ Stud 13(3):303–309
Gordon KB, Macrae IM, Carswell HV (2005) Effects of 17beta-oestradiol on cerebral ischaemic damage and lipid peroxidation. Brain Res 2:155–162
Swartz KR, Fee DB, Joy KM et al (2007) Gender differences in spinal cord injury are not estrogen-dependent. J Neurotrauma 24(3):473–480
Nilsen J (2008) Estradiol and neurodegenerative oxidative stress. Front Neuroendocrinol 29(4):463–475
Joosten HF, van Acker FA, van den Dobbelsteen DJ et al (2004) Genotoxicity of hormonal steroids. Toxicol Lett 151(1):113–134
Acknowledgments
This work was supported by the National Research Council of Brazil (CNPq), and FINEP/Rede IBN 01.06.0842-00. Leonardo M. Crema was the recipient of a CAPES fellowship.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Crema, L.M., Diehl, L.A., Aguiar, A.P. et al. Effects of Chronic Restraint Stress and 17-β-Estradiol Replacement on Oxidative Stress in the Spinal Cord of Ovariectomized Female Rats. Neurochem Res 35, 1700–1707 (2010). https://doi.org/10.1007/s11064-010-0232-1
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-010-0232-1