Am J Perinatol 2021; 38(S 01): e351-e358
DOI: 10.1055/s-0040-1710352
Original Article

Resveratrol Relieves Hyperoxia-Induced Brain Injury in Neonatal Rats by Activating Sirt1

Lan Kang
1   Department of Newborn Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
,
Wenbin Dong
1   Department of Newborn Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
,
Xiaobin Li
2   Department of Burns and Plastic Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
,
Ying Ruan
1   Department of Newborn Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
,
Rong Zhang
1   Department of Newborn Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
› Author Affiliations
Funding This study received its financial support from National Natural Science Foundation of China (grant number 81571480 to W.D.).

Abstract

Objective Neonatal rats with hyperoxia-induced brain injury were treated with resveratrol to investigate its protective effects through analyzing changes in reactive oxygen species (ROS), Sirt1, p53, and acetylated p53 levels.

Study Design Neonatal rats were randomly divided into hyperoxia and resveratrol intervened groups. Rats in both groups were placed in a hyperoxia chamber for 7 days to induce hyperoxia-induced brain injury. The rats in the resveratrol intervened group were administered resveratrol 60 μg/g body weight daily, whereas those in the hyperoxia group were administered a dimethyl sulfoxide-based solvent. Brain tissues were collected, and hematoxylin and eosin (H&E) and TUNEL staining, ROS measurements, real time-polymerase chain reaction, and western blotting were performed.

Results H&E and TUNEL staining revealed increased cell damage and apoptosis in brain tissue from hyperoxia-exposed animals compared with the findings in animals in the resveratrol intervened group. Real time-polymerase chain reaction and western blotting identified increases in Sirt1 expression and decreases in p53 expression in the resveratrol intervened group. In addition, acetylated p53 protein expression was lower in the intervened group than in the hyperoxia group.

Conclusion Resveratrol alleviated brain apoptosis induced by hyperoxia in neonatal rats by upregulating Sirt1-mediated pathways, suggesting its potentially beneficial role in the treatment of brain injury induced by hyperoxia.



Publication History

Received: 11 December 2019

Accepted: 30 March 2020

Article published online:
01 May 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Lea CL, Smith-Collins A, Luyt K. Protecting the premature brain: current evidence-based strategies for minimising perinatal brain injury in preterm infants. Arch Dis Child Fetal Neonatal Ed 2017; 102 (02) F176-F182
  • 2 Volpe JJ. Perinatal brain injury: from pathogenesis to neuroprotection. Ment Retard Dev Disabil Res Rev 2001; 7 (01) 56-64
  • 3 Manuck TA, Rice MM, Bailit JL. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Preterm neonatal morbidity and mortality by gestational age: a contemporary cohort. Am J Obstet Gynecol 2016; 215 (01) 103.e1-103.e14
  • 4 Voss W, Hobbiebrunken E, Ungermann U, Wagner M, Damm G. The development of extremely premature infants. Dtsch Arztebl Int 2016; 113 (51-52): 871-878
  • 5 Rizzo A, Roscino MT, Binetti F, Sciorsci RL. Roles of reactive oxygen species in female reproduction. Reprod Domest Anim 2012; 47 (02) 344-352
  • 6 Ozsurekci Y, Aykac K. Oxidative stress related diseases in newborns. Oxid Med Cell Longev 2016; 2016: 2768365
  • 7 Abdel Ghany EA, Alsharany W, Ali AA, Youness ER, Hussein JS. Anti-oxidant profiles and markers of oxidative stress in preterm neonates. Paediatr Int Child Health 2016; 36 (02) 134-140
  • 8 Deuber C, Terhaar M. Hyperoxia in very preterm infants: a systematic review of the literature. J Perinat Neonatal Nurs 2011; 25 (03) 268-274
  • 9 Reynolds RH, Petersen MH, Willert CW. et al. Perturbations in the p53/miR-34a/SIRT1 pathway in the R6/2 Huntington's disease model. Mol Cell Neurosci 2018; 88: 118-129
  • 10 Tu W, Zhang Q, Liu Y. et al. Fluoride induces apoptosis via inhibiting SIRT1 activity to activate mitochondrial p53 pathway in human neuroblastoma SH-SY5Y cells. Toxicol Appl Pharmacol 2018; 347: 60-69
  • 11 Andrade S, Ramalho MJ, Pereira MDC, Loureiro JA. Resveratrol brain delivery for neurological disorders prevention and treatment. Front Pharmacol 2018; 9: 1261
  • 12 Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem 2005; 280 (17) 17187-17195
  • 13 Kim YE, Park WS, Sung DK. et al. Intratracheal transplantation of mesenchymal stem cells simultaneously attenuates both lung and brain injuries in hyperoxic newborn rats. Pediatr Res 2016; 80 (03) 415-424
  • 14 Xu W, Zhao Y, Zhang B. et al. Resveratrol attenuates hyperoxia-induced oxidative stress, inflammation and fibrosis and suppresses Wnt/β-catenin signalling in lungs of neonatal rats. Clin Exp Pharmacol Physiol 2015; 42 (10) 1075-1083
  • 15 Blencowe H, Cousens S, Oestergaard MZ. et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 2012; 379 (9832): 2162-2172
  • 16 Moore T, Hennessy EM, Myles J. et al. Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure studies. BMJ 2012; 345: e7961
  • 17 van Haastert IC, Groenendaal F, Uiterwaal CS. et al. Decreasing incidence and severity of cerebral palsy in prematurely born children. J Pediatr 2011; 159 (01) 86-91.e1
  • 18 Poulose N, Raju R. Sirtuin regulation in aging and injury. Biochim Biophys Acta 2015; 1852 (11) 2442-2455
  • 19 Zhao X, Liu Y, Zhu G. et al. SIRT1 downregulation mediated Manganese-induced neuronal apoptosis through activation of FOXO3a-Bim/PUMA axis. Sci Total Environ 2019; 646: 1047-1055
  • 20 Ferguson D, Shao N, Heller E. et al. SIRT1-FOXO3a regulate cocaine actions in the nucleus accumbens. J Neurosci 2015; 35 (07) 3100-3111
  • 21 Kang L, Dong W, Ruan Y, Zhang R, Wang X. The molecular mechanism of Sirt1 signaling pathway in brain injury of newborn rats exposed to hyperoxia. Biol Pharm Bull 2019; 42 (11) 1854-1860
  • 22 Joao Tomé-Carneiro ML, González-Sarrías A, Tomás-Barberán FA, García-Conesa MT, Espín JC. Resveratrol and clinical trials_ the crossroad from in vitro studies to human evidence. Curr Pharm Des 2013; 19: 6064-6093
  • 23 Anastácio JR, Netto CA, Castro CC. et al. Resveratrol treatment has neuroprotective effects and prevents cognitive impairment after chronic cerebral hypoperfusion. Neurol Res 2014; 36 (07) 627-633
  • 24 Cao W, Dou Y, Li A. Resveratrol boosts cognitive function by targeting Sirt1. Neurochem Res 2018; 43 (09) 1705-1713
  • 25 Venturini CD, Merlo S, Souto AA, Fernandes MdaC, Gomez R, Rhoden CR. Resveratrol and red wine function as antioxidants in the nervous system without cellular proliferative effects during experimental diabetes. Oxid Med Cell Longev 2010; 3 (06) 434-441
  • 26 Girbovan C, Plamondon H. Resveratrol downregulates type-1 glutamate transporter expression and microglia activation in the hippocampus following cerebral ischemia reperfusion in rats. Brain Res 2015; 1608: 203-214
  • 27 Singleton RH, Yan HQ, Fellows-Mayle W, Dixon CE. Resveratrol attenuates behavioral impairments and reduces cortical and hippocampal loss in a rat controlled cortical impact model of traumatic brain injury. J Neurotrauma 2010; 27 (06) 1091-1099
  • 28 Shao AW, Wu HJ, Chen S, Ammar AB, Zhang JM, Hong Y. Resveratrol attenuates early brain injury after subarachnoid hemorrhage through inhibition of NF-κB-dependent inflammatory/MMP-9 pathway. CNS Neurosci Ther 2014; 20 (02) 182-185
  • 29 Li XM, Zhou MT, Wang XM, Ji MH, Zhou ZQ, Yang JJ. Resveratrol pretreatment attenuates the isoflurane-induced cognitive impairment through its anti-inflammation and -apoptosis actions in aged mice. J Mol Neurosci 2014; 52 (02) 286-293
  • 30 Zhao YN, Li WF, Li F. et al. Resveratrol improves learning and memory in normally aged mice through microRNA-CREB pathway. Biochem Biophys Res Commun 2013; 435 (04) 597-602
  • 31 Zhang L, Tu R, Wang Y. et al. Early-Life Exposure to Lead Induces Cognitive Impairment in Elder Mice Targeting SIRT1 Phosphorylation and Oxidative Alterations. Front Physiol 2017; 8: 446
  • 32 Meng Z, Li J, Zhao H. et al. Resveratrol relieves ischemia-induced oxidative stress in the hippocampus by activating SIRT1. Exp Ther Med 2015; 10 (02) 525-530