Abstrakt
Background: Sleep deprivation affects a significant proportion of the global population. It has been reported to induce oxidative stress in the testes and reduce serum testosterone levels. Exogenous anti-oxidants have been known to prevent damages and diseases associated with oxidative stress but there is dearth of knowledge on their effectiveness during sleep deprivation.
Aim: This study was designed to investigate the effects of two antioxidants; melatonin and vitamin E on serum testosterone concentration in sleep deprived male Wistar rats.
Methods: Thirty (30) male Wistar rats were used for this study. Animals were divided into six (6) groups (n=5). Group 1 was the control, group 2 rats were sleep deprived, group 3 received vitamin E (200mg/kg bwt) only, group 4 rats received vitamin E and were sleep deprived, group 5 received melatonin only (10mg/kg bwt), and group 6 rats received melatonin (10mg/kg bwt) and were sleep deprived. Sleep deprivation was induced using the modified multiple platform technique. Body weights were taken on days 7, 14 and 21. Blood was collected at sacrifice and serum was obtained for analyses of testosterone, corticosterone and melatonin. Testicular malondialdehyde, superoxide dismutase and catalase levels were determined by the methods of Adam-Vizi and Seregi (1982), Misra and Fridovich (1972), and Sinha, (1972) respectively. Data obtained were analyzed using one way ANOVA and p<0.05 was considered significant.
Results: Serum testosterone (nmol/l) of the sleep deprived animals (0.6±0.3) reduced significantly (p<0.05) compared with control group (3.3±0.04), sleep deprived+vitamin E group (2.8±0.5) and sleep deprived+melatonin group (2.0±0.3). Also, melatonin+sleep deprived group had reduced testosterone compared with control. There were no significant changes in the serum corticosterone (nmol/l) and melatonin levels in all the groups compared with the sleep deprived group. However, corticosterone was increased in the sleep deprived+vitamin E group (51.6±20.5) compared with control (6.3±0.6) Sleep deprived group had increased testicular malondialdehyde (MDA) (1.6±0.1unit/mg), superoxide dismutase (SOD) (3.2±0.2unit/mg), and catalasel evels(44.3±1.1unit/mg) compared with control (0.9±0.0μ/mg). MDA, and catalase were significantly reduced in sleep deprived+vitamin E (1.1±0.2, 2.4±0.3, 39±1.0unit/mg)compared with sleep deprived while melatonin alone had increased MDA level (1.7±0.2unit/mg) compared with control. SOD in the sleep deprived+melatonin group (2.7±0.2μ/mg) as compared with control increased (p<0.05) while MDA and catalase levels as compared with control and sleep deprived groups showed no difference. Histological findings showed that the pathology in the testes of sleep deprived rats was ameliorated by vitamin E.
Conclusion: Vitamin E had a more potent effect than melatonin in maintaining testosterone level in sleep deprived Wistar rat.
Keywords: Sleep deprivation, testosterone, oxidative stress, melatonin, malondealdehyde
Résumé
Contexte: La privation de sommeil affecte une proportion importante de la population Global. Il a été rapporté pour induire un stress oxydatif dans les testicules et de réduire les niveaux du sérum testostérone. Les antioxydantes exogènes ont été connus pour prévenir les dégâts et les maladies associées au stress oxydatif, mais il ya une insuffisance de connaissances sur leur efficacité lors de la privation de sommeil.
Objectif: Cette étude a
été conçue pour étudier les effets de deux anti-oxydantes; la mélatonine et la vitamine E sur la concentration du
sérum testostérone chez les rats Wistar mâles privés de sommeil.
Méthodes: Trente (30) rats Wistar mâles ont été utilisés pour cette étude. Les animaux ont été divisés en six (6) groupes (n = 5). Groupe 1 était le contrôle, les rats du groupe 2 ont été privés de sommeil, le groupe 3 a reçu la vitamine E (200 mg / kg de poids corporel) seulement, groupe 4 les rats ont reçu la vitamine E et ont été privés de sommeil, groupe 5 a seulement reçu la mélatonine (10 mg / kg de poids corporel), et les rats de groupe 6 ont reçu de la mélatonine (10 mg / kg de poids corporel) et ont été privés de sommeil. La privation de sommeil a été induite en utilisant la technique à multiple plate-forme modifiée. Les poids corporels ont été prélevés aux jours 7, 14 et 21. Le sang a été recueilli au moment du sacrifice et le sérum a été obtenu pour les analyses de la testostérone, la corticostérone et la mélatonine. La malondealdehyde testiculaire, la super-oxyde dismutase et la catalase ont été déterminées par les méthodes d’Adam-Vizi et Seregi (1982), Misra et Fridovich (1972), et Sinha, (1972) respectivement. Les données obtenues ont été analysées en utilisant ANOVA à un facteur et p <0,05 était considérée comme significative.
Résultats: Le sérum testostérone (nmol / L) des animaux privés de sommeil (0,6 ± 0,3) réduit de façon significative (p <0,05) par rapport au groupe témoin (3,3 ± 0,04), groupe de manque de sommeil + vitamine E (2,8 ± 0,5) et groupe privé de sommeil + mélatonine (2,0 ± 0,3). En outre, le groupe, mélatonine + privé de sommeil avait réduit de testostérone par rapport au témoin. Il n’y avait pas de changements significatifs dans le sérum corticostérone (nmol / l) et les niveaux de mélatonine dans tous les groupes par rapport au groupe de manque de sommeil. Cependant, la corticostérone a été augmenté dans le groupe privé de sommeil + vitamine E (51,6 ± 20,5) par rapport au témoin (6,3 ± 0,6). Le groupe privé de sommeil avait la malondealdehyde testiculaire (MDA) (1,6 ± 0.1μ / mg), le super-oxyde dismutase (SOD) (3,2 ± 0.2μ / mg), les niveaux de catalase (44,3 ± 1.1μ / mg) augmentées par rapport au témoin (0,9 ± 0.0μ / mg). MDA, SOD et la catalase avaient significativement réduit dans le group privé de sommeil + vitamine E (1,1 ± 0,2; 2,4 ± 0,3; 39 ± 1.0μ / mg) tandis que seulement la mélatonine avait un niveau augmenté en MDA (1,7 ± 0.2μ / mg) par rapport au contrôle. SOD dans le groupe privé de sommeil + mélatonine (2,7 ± 0.2μ / mg) par rapport au contrôle a augmenté (p <0,05), tandis que les niveaux de MDA et de catalase par rapport aux groupes de contrôle et privés de sommeil n’ont pas montré de différence. Les résultats histologiques ont montré que la pathologie des testicules des rats privés de sommeil a été améliorée par la vitamine E.
Conclusion: La vitamine E a eu un effet plus puissant que la mélatonine dans le maintien du niveau de testostérone dans le rat Wistar privé de sommeil.
Mots-clés: privation de sommeil, testostérone, stress oxydatif, l mélatonine, malondealdehyde
Abstract was presented on the 22nd October at the poster session of the IUPS Regional Teaching and Research Workshop and
XXXIVTH PSN Scientific Conference.
Correspondence: Dr. O.O. Akindele, Department of Physiology, College of Medicine, University of Ibadan, Nigeria. E-mail: oo.akindele@ui.edu.ng; opeyemiakindele@gmail.com
Bibliografia
Andersen ML, Alvarenga TF, Mazaro-Costa R, Hachul HC and Tufik S. The association of testosterone, sleep, and sexual function in men and women. Brain Res 2011; 1416: 80–104.
Maquet, P. The role of sleep in learning and memory. Science 2001; 294:1048–1052.
Martin K, Stanchina M, Kouttab N, et al. Circulating endothelial cells and endothelial progenitor cells in obstructive sleep apnea. Lung. 2008; 186: (3) 145–150.
CDC (Centres for Disease Control and Prevention) Percentage of adults who reported an average of 6 hours of sleep per 24-hour period, by sex and age group—United States, 1985 and 2004. Morbidity and Mortality Weekly Report. 2005; 54(37): 933.
Goel N and Dinges DF. Behavioural and genetic markers of sleepiness. J Clin Sleep Med 2011; 7 (5): 19-21.
Tufik S, Andersen ML, Bittencourt LRA and de Mello MT. Paradoxical sleep deprivation: neurochemical, hormonal and behavioural alterations. Evidence from 30 years of research. An. Acad. Bras. Ciênc. 2009; 81: 83
Cortés-Gallegos V, CastaZeda G, Alonso R et al. Sleep Deprivation reduces circulating Adrogen in Healthy Men. Arch Androl 1983; 33-37
Luboshitzky R, Aviv A, Hefetz A et al. Decreased pituitary-gonadal secretion in men with obstructive sleep apnea. J Clin Endocrinol Metab 2002; 87 (7): 3394–3398.
Chang HM, Mai FD, Chen BJ et al. Sleep deprivation predisposes liver to oxidative stress and phospholipid damage: A quantitative molecular imaging study. J. Anat 2008; 212(3): 295-305
D’almeida V, Lobo LL, Hipólide DC, et al. Sleep deprivation induces brain region-specific decreases in glutathione levels. Neuroreport 1998; 9: 2853-2856.
Everson CA, Laatsch CD and Hogg N. Antioxidant defense responses to sleep loss and sleep recovery.Am J Physiol Regul Integr Comp Physiol. 2005; 288(2): 374-383.
You JM, Yun SJ, Nam KN, et al. Mechanism of glucocorticoid-induced oxidative stress in rat hippocampal slice cultures. Can J Physiol Pharmacol. 2009;87(6): 440-447.
Feng YL and Tang XL. Effects of Glucocorticoid-induced oxidative stress on the expression of Cbfa1. Chemico-Biological Interactions 2014; 207: 26-31
Mirescu C, Peters JD, Noiman L and Gould E. Sleep deprivation inhibits adult neurogenesis in the hippocampus by elevating glucocorticoids. PNAS 2006; 103(50): 19170-19175
El-Tohamy MM (2012). The mechanisms by which Oxidative Stress and Free Radical Damage produces Male infertility. Life Sci J; 2012; 9: 674-688.
Sies H. Oxidative stress: oxidants and antioxidants.Exp Physiol. 1997 ;82(2): 291-295
Ahmad R and Haldar C. Photoperiodic regulation of MT1 and MT2 melatonin receptor expression in spleen and thymus of a tropical rodent Funambulus pennanti during reproductively active and inactive phases. Chronobiology international 2010; 27(3) 446-462.
Yadav S and Haldar C: Reciprocal interaction between melatonin receptors (Mel (1a), Mel(1b), and Mel(1c)) and androgen receptor (AR) expression in immunoregulation of a seasonally breeding bird, Perdicula asiatica: role of photoperiod. J Photochem Photobiol 2013; 5: 52-60.
Hardeland R. Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance.Endocrine. 2005; 27(2): 119-130.
Zhang HM and Zhang Y. Melatonin: a well-documented antioxidant with conditional pro-oxidant actions. J Pineal Res. 2014; 57(2): 131-146
Zhang L, Zhang HQ, Liang XY, et al. Melatonin ameliorates cognitive impairment induced by sleep deprivation in rats: role of oxidative stress, BDNF and CaMKII.Behav Brain Res. 2013; 256: 72-81.
Kumar A and Singh A. Possible involvement of GABAergic mechanism in protective effect of melatonin against sleep deprivation-induced behaviour modification and oxidative damage in mice.Fundam Clin Pharmacol. 2009; 23(4): 439-448.
Tasdemir S, Samdanci E, Parlakpinar H et al. Effects of pinealectomy and exogenous melatonin on the brains, testes, duodena and stomachs of rats. Eur. Rev. Med. Pharmacol. Sci. 2012; 16: 860-866. .
Bejarano I, Monllor F, Marchena AM et al. Exogenous melatonin supplementation prevents oxidative stress-evoked DNA damage in human spermatozoa. J. Pineal Res 2014; 57 (3): 333-339.
Regina BF and Maret GT. Vitamin E: function and metabolism. The FASEB Journal 1999; 13 (10): 1145-1155.
Guide for the Care and Use of Laboratory Animals, NIH Publication revised 1996; No. 85-23.
Rashed RA, Mohamed IK and El-Alfy SH. Effects of Two Different Doses of Melatonin on the Spermatogenic Cells of Rat Testes: A Light and Electron Microscopic Study. Egypt J. Histol. 2010; 33 (4): 819-835.
Nunes Jr Gp and Tufik S. Validation of the modified multiple platform method (MMP) of paradoxical sleep deprivation in rats. Sleep Res 1994; 23: 419
Herck VH, Baumans V, Brandt CJWM et al. Blood sampling from the retro-orbital plexus, the saphenous vein and the tail vein in rats: comparative effects on selected behavioural and blood variables. Laboratory Animal Refinement and Enrichment Forum. Animal Technology and Welfare 2001; 4: 00-102
Adam-Vizi, V. and Seregi M. Receptor dependent stimulatory effect of noradrenaline on Na+/K+ ATPase in rat brain homogenate: Role of lipid peroxidation. Biochem. Pharmacol, 1982; 31: 2231-2236.
Misra HP and Fridovich I. The role of superoxide anion in the auto-oxidation of epinephrine and a simple assay for superoxide dismutase. J. Biol. Chem. 1972; 247 (10): 3170 – 3175.
Sinha AK. Anal Biochem. Colorimetric assay of catalase.1972 ;47(2):389-394
Andersen ML, Bignotto M, Machado RB and Tufik S. Different stress modalities result in distinct steroid hormone responses by male rats. Braz J Med Biol Res. 2004; 37(6) 791-797.
Venâncio DP Andersen ML,Vilamaior PSL et al. Sleep Deprivation Alters Rat Ventral Prostate Morphology, Leading to Glandular Atrophy: A Microscopic Study Contrasted with the Hormonal Assays. J Biomed Biotechnol 2012; 2012.
Oh MM, Kim JW, Jin MH, Kim JJ and Moon DG. Influence of paradoxical sleep deprivation and sleep recovery on testosterone level in rats of different ages. Asian J Androl 2012; 14: 330-334.
Wu JL, Wu RS, Yang JG et al. Effects of sleep deprivation on serum testosterone concentrations in the rat. Neuroscience Letters. 2011; 494 (2): 124–129.
Walter F and Addis T. Organ Work and Organ Weight. JEM, 1939; 69(3):467-483
Hayes AW. Principles and Methods of Toxicology. 2007; 5th Edition: 604
Stephensen R, Chu KM and Lee J. Prolonged deprivation of sleep-like rest raises metabolic rate in the Pacific beetle cockroach, Diploptera punctata (Eschscholtz)J. Exp. Biol; 2007; 210: 2540-2547.
Everson CA, Bergmann BM, and Rechtschaffen. Sleep Deprivation in the Rat: III. Total Sleep Deprivation. Sleep 2005; 12(1):13-21.
Peder M, Porkka-Heiskanen T, Laakso ML and Johansson G. Rapid eye movement sleep deprivation depresses plasma FSH and LH in castrated rats. Pysiol Behav. 1989; 45(6):1167-1170.
Orr TE and Mann DR. Effects of restraint stress on LH and testosterone concentrations, Leydig cell LH/HCG receptors, captures and in vitro testicular steroidogenesis in adult rats. Horm Behav. 24: 324.
Monder C, Sakai RR, Miroff Y, et al. Reciprocal changes in plasma corticosterone and testosterone in stressed male rats maintained in a visible burrow system: evidence for a mediating role of testicular 11 beta-hydroxysteroid dehydrogenase. Endocrinology. 1994; 134:1193-1198.
Rivier C, Rivier J and Vale W. Stress-induced inhibition of reproductive functions: Role of endogenous corticotropin-releasing factor. Science. 1986; 231: 607–609.
Rivier C and Rivest S. Effect of stress on the activity of the hypothalamic-pituitary-gonadal axis: Peripheral and central mechanisms. Biol Reprod 1991; 45:523–532.
Abd El-Aziz EA and Mostafa DG. Impact of Sleep Deprivation and Sleep Recovery on Reproductive Hormones and Testicular Oxidative Stress in Adult Male Rats. AAMJ 2012; 10 (3)1
Thamaraiselvi K, Mathangi DC and Subhashini AS. Effect of increase in duration of REM sleep deprivation on lipid peroxidation. Int J Biol Med Res. 2012; 3(2): 1754-1759.
Aitken RJ and Roman SD; Antioxidant systems and oxidative stress in the testes. Adv Exp Med Biol 2008; 636: 154-171.