Effect of sleep deprivation on the liver, kidney and heart: histological and immunohistochemical study


  • Medhat Taha Department of Anatomy and Embryology, Faculty of Medicine, University of Mansoura, Mansoura, Egypt
  • Hagar Y. Rady Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
  • Nouran K. Olama Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt




Sleep deprivation, Oxidative stress, Melatonin, GFAP, P53


Background: Sleep deprivation is verging on a public health epidemic. It induced mild organ injuries through oxidative stress. The present study aimed at evaluating possible histopathological and immunohistochemical alterations caused by sleep deprivation on the liver, heart and kidney.

Methods: 36 Wistar senile male albino rats were divided into two groups; control and experimental. Experimental rats were placed in a plastic cage, with grid floor placed inside it. The cage was filled with water to 1 cm below the grid surface. The stainless-steel rods of the grid were set 2 cm apart from each other. Loss of muscle tone associated with sleep caused them to touch the water and wake up. At the end of the experiment, animals were sacrificed by decapitation on days 1, 3 and 5. Liver, kidney and heart were obtained and dissected.  

Results: In SSD1 group, liver cells showed early stage of hepatic steatosis while mucolipidosis within hepatocytes was detected in SSD3 and the degree of steatosis increased in SSD5. Renal glomerular congestion was detected in SSD1. In SSD3 vascular congestion of glomerular tufts and apoptosis of the lining tubular epithelium was seen. Renal casts were formed in SSD5. In SSD1 lysis of myocardial fibrils was seen. Myocardial fibers degeneration represented by increase sarcoplasmic eosinophilia in SSD3. Sarcoplasmic vacuolation and nuclear chromatolysis increased in SSD5. Staining with GFAP and P53 showed various results among the liver, heart and kidney.

Conclusions: Sleep deprivation might induce multiple organ injury through oxidative stress causing altered histological appearance.


Metrics Loading ...


Grandner M, Chakravorty S, Perlis M, Oliver L, Gurubhagavatula I. Habitual sleep duration associated with self-report and objectively determined cardiometabolic risk factors. Sleep Med. 2014;15:42-50.

Lima A, de Bruin V, Rios E, de Bruin P. Differential effects of paradoxical sleep deprivation on memory and oxidative stress. Naunyn Schmiedebergs Arch Pharmacol. 2014;387:399-406.

Bixler E. Sleep and society: an epidemiological perspective. Sleep Med. 2009;10:3-9.

National Sleep Foundation. Sleep in America Poll Summary of Findings. Washington, DC, 2005.http://sleepfoundation.org/sleep-polls-data/sleep-in-america-poll/2005-adult-sleep-habits-and-styles. Accessed 24 December 2017.

Gangwisch J, Heymsfield S, Boden-Albala B, Buijs R, Kreier F, Opler M, et al. Sleep duration associated with mortality in elderly, but not middle- aged, adults in a large US sample. Sleep. 2008;31:1087-96.

Wolk R, Gami A, Garcia-Touchard A, Somers V. Sleep and cardiovascular disease. Curr Probl Cardiol. 2005;30:625-62.

Dang-Vu T, Desseilles M, Peigneux P, Maquet P. A role for sleep in brain plasticity. Pediatr Rehabil. 2006;9:98-118.

Gangwisch J, Heymsfield S, Boden-Albala B, Buijs R, Kreier F, Pickering T, et al. Sleep duration as a risk factor for diabetes incidence in a large US sample. Sleep. 2007;30:1667-73.

Silva R, Abilio V, Takatsu A, Kameda S, Grassl C, Chehin A, et al. Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Neuropharmacol. 2004;46:895–903.

Schultes B, Schmid S, Peters A, Born J, Fehm H. Sleep loss and the development of diabetes: a review of current evidence. Exp Clin Endocrinol Diabetes. 2005;113:563–7.

Steptoe A, Peacey V, Wardle J. Sleep duration and health in young adults. Arch Intern Med. 2006;166:1689-92.

Taheri S, Lin L, Austin D, Young T, Mignot E. Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med. 2004;1:62.

Halperin D. Environmental noise and sleep disturbances: a threat to health? Sleep Science. 2014;7(4):209-12.

Cappuccio F, Cooper D, D’Elia L, Strazzullo P, Miller M. Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies. Eur Heart J. 2011;32(12):1484-92.

Everson C, Laatsch C, Hogg N. Antioxidant defense responses to sleep loss and sleep recovery. Am J Physiol Regul Integr Comp Physiol. 2005;288:374-83.

McEwen B. Sleep deprivation as a neurobiologic and physiologic stressor: Allostasis and allostatic load. Metabolism. 2006;55:20-3.

Chang H, Wu U, Lin T, Lan C, Chien W, Huang W, et al. Total sleep deprivation inhibits the neuronal nitric oxide synthase and cytochrome oxidase reactivities in the nodose ganglion of adult rats. J Anat. 2006;209:239-50.

Turrens J. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552:335-44.

Droge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002;82:47-95.

Reimund E. The free radical flux theory of sleep. Med Hypotheses. 1994;43:231-3.

Shinomiya K, Shigemoto Y, Okuma C, Mio M, Kamei C. Effects of short-acting hypnotics on sleep latency in rats placed on grid suspended over water European Journal of Pharmacol. 2003;460:139–44.

Baratta J, Ngo A, Lopez B, Kasabwalla N, Longmuir K, Robertson R. Cellular organization of normal mouse liver: a histological, quantitative immunocytochemical, and fine structural analysis. Histochem Cell Biol. 2009;131:713–26.

Panasiuk A, Dzieciol J, Panasiuk B, Prokopowicz D. Expression of p53, Bax and Bcl-2 proteins in hepatocytes in non-alcoholic fatty liver disease. World J Gastroenterol. 2006;12(38):6198-202.

Rabek J, Boylston III W, Papaconstantinou J. Carbonylation of ER. chaperone proteins in aged mouse liver. Biochem Biophys Res Commun. 2003;305:566–72.

Naidoo N, Ferber M, Master M, Zhu Y, Pack A. Aging impairs the unfolded protein response to sleep deprivation and leads to proapoptotic signaling. J Neurosci. 2008;28(26):6539-48.

Periasamy S, Hsu D, Fu Y, Liu M. Sleep deprivation-induced multi-organ injury: role of oxidative stress and inflammation. XCLI Journal. 2015;14:672-83.

Gopalakrishnan A, Ji L, Cirelli C. Sleep deprivation and cellular responses to oxidative stress. Sleep. 2004;27:27-35.

Sun H, Huang F, Qu S. Melatonin. A potential intervention for hepatic steatosis. Lipids in Health Dis. 2015;14:75.

Reiter R, Paredes S, Korkmaz A, Manchester L, Tan D. Melatonin in relation to the “strong” and “weak” versions of the free radical theory of aging. Adv Med Sci. 2008;53(2):119-29.

Mauriz J, Molpeceres V, García-Mediavilla M, González P, Barrio J, González-Gallego J. Melatonin prevents oxidative stress and changes in antioxidant enzyme expression and activity in the liver of aging rats. J Pineal Res. 2007;42(3):222–30.

Gitto E, Tan D, Reiter R, Karbownik M, Manchester L, Cuzzocrea S, et al. Individual and synergistic antioxidative actions of melatonin: studies with vitamin E, vitamin C, glutathione and desferrioxamine (desferoxamine) in rat liver homogenates. J Pharm Pharmacol. 2001;53(10):1393–401.

Mayo J, Tan D, Sainz R, Lopez-Burillo S, Reiter R. Oxidative damage to catalase induced by peroxyl radicals: functional protection by melatonin and other antioxidants. Free Radic Res. 2003;37(5):543–53.

Solis-Munoz P, Solís-Herruzo J, Fernández-Moreira D, Gómez-Izquierdo E, García-Consuegra I, Muñoz-Yagüe T, et al. Melatonin improves mitochondrial respiratory chain activity and liver morphology in ob/ob mice. J Pineal Res. 2011;51(1):113–23.

Copinschi G. Metabolic and endocrine effects of sleep deprivation. Essent Psychopharmacol. 2005;6:341-7.

Martino T, Oudit G, Herzenberg A, Tata N, Koletar M, Kabir G, et al. Circadian rhythm disorganization produces profound cardiovascular and renal disease in hamsters. Am J Physiol. 2008;294:1675-83.

Penev P, Kolker D, Zee P, Turek F. Chronic circadian desynchronization decreases the survival of animals with cardiomyopathic heart disease. Am J Physiol, 1998;275:2334-7.

Sahna E, Deniz E, Aksulu H. Myocardial ischemia-reperfusion injury and melatonin. Anadolu Kardiyol Derg. 2006;6(2):163-8.






Original Research Articles