Curcumin attenuates hypoxic‑ischemic brain injury in neonatal rats through induction of nuclear factor erythroid‑2‑related factor 2 and heme oxygenase‑1

Cui,Xiaolu; Song,Hongquan; Su,Jie

doi:10.3892/etm.2017.4683

Curcumin attenuates hypoxic‑ischemic brain injury in neonatal rats through induction of nuclear factor erythroid‑2‑related factor 2 and heme oxygenase‑1

Authors:
- Xiaolu Cui
- Hongquan Song
- Jie Su
View Affiliations

Affiliations: Department of Rehabilitation Medicine, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, P.R. China, Department of Spleen and Stomach, Affiliated Hospital of Shandong University of TCM, Jinan, Shandong 250013, P.R. China, Department of Cadres and Health Care, The Second Affiliated Hospital of Shandong University of TCM, Jinan, Shandong 250001, P.R. China
Published online on: June 27, 2017 https://doi.org/10.3892/etm.2017.4683
Pages: 1512-1518
Copyright: © Cui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Curcumin has previously demonstrated anti‑inflammatory, anti‑infective and immuno‑suppressive effects. In the present study, whether the attenuating effects of curcumin against hypoxic‑ischemic brain injury in neonatal rats are mediated via nuclear factor erythroid‑2‑related factor 2 (Nrf2) and heme oxygenase‑1 (HO‑1) was investigated. A model of hypoxic‑ischemic brain injury was created using 1‑week‑old Sprague Dawley rats (weight, 52±1 g). The model rats were treated with 150 mg/kg curcumin by gavage for 3 days. Malondialdehyde levels, and superoxide dismutase and caspase‑3 activities were assayed using commercial kits and western blot analysis was used to measure inducible nitric oxide synthase (iNOS), Nrf2 and HO‑1 expression levels. Treatment with curcumin effectively reduced the brain injury score, increased myelin basic protein (MBP) expression and increased the quantity of neuronal cells in neonatal rats with hypoxic‑ischemic brain injury. Furthermore, treatment with curcumin significantly attenuated the changes in SOD activity and MDA levels and suppressed the iNOS protein expression induced in neonatal rats by hypoxic‑ischemic brain injury. Treatment with curcumin significantly increased Nrf2 and HO‑1 expression in the neonatal rats with hypoxic‑ischemic brain injury. The present study indicated that curcumin attenuates hypoxic‑ischemic brain injury in neonatal rats through the induction of Nrf2 and HO‑1.

View Figures

View References

1	Shankaran S, Laptook AR, Pappas A, McDonald SA, Das A, Tyson JE, Poindexter BB, Schibler K, Bell EF, Heyne RJ, et al: Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy: A randomized clinical trial. JAMA. 312:2629–2639. 2014. View Article : Google Scholar : PubMed/NCBI
2	Kracer B, Hintz SR, Van Meurs KP and Lee HC: Hypothermia therapy for neonatal hypoxic ischemic encephalopathy in the state of California. J Pediatr. 165:267–273. 2014. View Article : Google Scholar : PubMed/NCBI
3	Re L, Martinez-Sãnchez G, Bordicchia M, Malcangi G, Pocognoli A, Morales-Segura MA, Rothchild J and Rojas A: Is ozone pre-conditioning effect linked to Nrf2/EpRE activation pathway in vivo? A preliminary result. Eur J Pharmacol. 742:158–162. 2014. View Article : Google Scholar : PubMed/NCBI
4	Wu Z, Uchi H, Morino-Koga S, Shi W and Furue M: Z-ligustilide ameliorated ultraviolet B-induced oxidative stress and inflammatory cytokine production in human keratinocytes through upregulation of Nrf2/HO-1 and suppression of NF-κB pathway. Exp Dermatol. 24:703–708. 2015. View Article : Google Scholar : PubMed/NCBI
5	Sasaki H, Suzuki A, Shitara M, Hikosaka Y, Okuda K, Moriyama S, Yano M and Fujii Y: Polymorphisms of NRF2 gene correlated with decreased FEV1 in lung cancers of smokers. Biomed Rep. 1:484–488. 2013.PubMed/NCBI
6	Barnett M, Hall S, Dixit M and Arany I: Simvastatin attenuates oleic acid-induced oxidative stress through CREB-dependent induction of heme oxygenase-1 in renal proximal tubule cells. Pediatr Res. 79:243–250. 2016. View Article : Google Scholar : PubMed/NCBI
7	Lin SH, Song W, Cressatti M, Zukor H, Wang E and Schipper HM: Heme oxygenase-1 modulates microRNA expression in cultured astroglia: Implications for chronic brain disorders. Glia. 63:1270–1284. 2015. View Article : Google Scholar : PubMed/NCBI
8	Morita K, Itoh M, Nishibori N, Her S and Lee MS: Spirulina non-protein components induce BDNF gene transcription via HO-1 activity in C6 glioma cells. Appl Biochem Biotechnol. 175:892–901. 2015. View Article : Google Scholar : PubMed/NCBI
9	Qian Y, Zhong P, Liang D, Xu Z, Skibba M, Zeng C, Li X, Wei T, Wu L and Liang G: A newly designed curcumin analog Y20 mitigates cardiac injury via anti-inflammatory and anti-oxidant actions in obese rats. PLoS One. 10:e01202152015. View Article : Google Scholar : PubMed/NCBI
10	Patel PB, Thakkar VR and Patel JS: Cellular effect of curcumin and citral combination on breast cancer cells: Induction of apoptosis and cell cycle arrest. J Breast Cancer. 18:225–234. 2015. View Article : Google Scholar : PubMed/NCBI
11	Jang EM, Choi MS, Jung UJ, Kim MJ, Kim HJ, Jeon SM, Shin SK, Seong CN and Lee MK: Beneficial effects of curcumin on hyperlipidemia and insulin resistance in high-fat-fed hamsters. Metabolism. 57:1576–1583. 2008. View Article : Google Scholar : PubMed/NCBI
12	Yeh CH, Chen TP, Wu YC, Lin YM and Lin P Jing: Inhibition of NFkappaB activation with curcumin attenuates plasma inflammatory cytokines surge and cardiomyocytic apoptosis following cardiac ischemia/reperfusion. J Surg Res. 125:109–116. 2005. View Article : Google Scholar : PubMed/NCBI
13	Liu L, Liu C, Lu Y, Liu L and Jiang Y: ER stress related factor ATF6 and caspase-12 trigger apoptosis in neonatal hypoxic-ischemic encephalopathy. Int J Clin Exp Pathol. 8:6960–6966. 2015.PubMed/NCBI
14	Kaandorp JJ, Benders MJ, Rademaker CM, Torrance HL, Oudijk MA, de Haan TR, Bloemenkamp KW, Rijken M, van Pampus MG, Bos AF, et al: Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study. BMC Pregnancy Childbirth. 10:82010. View Article : Google Scholar : PubMed/NCBI
15	Bell MJ, Adelson PD, Hutchison JS, Kochanek PM, Tasker RC, Vavilala MS, Beers SR, Fabio A, Kelsey SF and Wisniewski SR: Multiple Medical Therapies for Pediatric Traumatic Brain Injury Workgroup: Differences in medical therapy goals for children with severe traumatic brain injury-an international study. Pediatr Crit Care Med. 14:811–818. 2013. View Article : Google Scholar : PubMed/NCBI
16	Agut T, Leon M, Rebollo M, Muchart J, Arca G and Garcia-Alix A: Early identification of brain injury in infants with hypoxic ischemic encephalopathy at high risk for severe impairments: Accuracy of MRI performed in the first days of life. BMC Pediatr. 14:1772014. View Article : Google Scholar : PubMed/NCBI
17	Zhao M, Zhu P, Fujino M, Zhuang J, Guo H, Sheikh I, Zhao L and Li XK: Oxidative stress in hypoxic-ischemic encephalopathy: Molecular mechanisms and therapeutic strategies. Int J Mol Sci. 17(pii): E20782016. View Article : Google Scholar : PubMed/NCBI
18	Vasiljević B, Maglajlić-Djukić S, Gojnić M and Stanković S: The role of oxidative stress in perinatal hypoxic-ischemic brain injury. Srp Arh Celok Lek. 140:35–41. 2012. View Article : Google Scholar : PubMed/NCBI
19	Burchell SR, Dixon BJ, Tang J and Zhang JH: Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury. J Investig Med. 61:1078–1083. 2013. View Article : Google Scholar : PubMed/NCBI
20	Zhu C, Xu F, Fukuda A, Wang X, Fukuda H, Korhonen L, Hagberg H, Lannering B, Nilsson M, Eriksson PS, et al: X chromosome-linked inhibitor of apoptosis protein reduces oxidative stress after cerebral irradiation or hypoxia-ischemia through up-regulation of mitochondrial antioxidants. Eur J Neurosci. 26:3402–3410. 2007. View Article : Google Scholar : PubMed/NCBI
21	Perrone S, Tataranno LM, Stazzoni G, Ramenghi L and Buonocore G: Brain susceptibility to oxidative stress in the perinatal period. J Matern Fetal Neonatal Med. 28 Suppl 1:S2291–S2295. 2015. View Article : Google Scholar
22	Chang CC, Wang YH, Chern CM, Liou KT, Hou YC, Peng YT and Shen YC: Prodigiosin inhibits gp91(phox) and iNOS expression to protect mice against the oxidative/nitrosative brain injury induced by hypoxia-ischemia. Toxicol Appl Pharmacol. 257:137–147. 2011. View Article : Google Scholar : PubMed/NCBI
23	Sosunov SA, Ameer X, Niatsetskaya ZV, Utkina-Sosunova I, Ratner VI and Ten VS: Isoflurane anesthesia initiated at the onset of reperfusion attenuates oxidative and hypoxic-ischemic brain injury. PLoS One. 10:e01204562015. View Article : Google Scholar : PubMed/NCBI
24	Feng Y, Lu S, Wang J, Kumar P, Zhang L and Bhatt AJ: Dexamethasone-induced neuroprotection in hypoxic-ischemic brain injury in newborn rats is partly mediated via Akt activation. Brain Res. 1589:68–77. 2014. View Article : Google Scholar : PubMed/NCBI
25	Gao S, Zhou J, Liu N, Wang L, Gao Q, Wu Y, Zhao Q, Liu P, Wang S, Liu Y, et al: Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13. J Mol Cell Cardiol. 85:131–139. 2015. View Article : Google Scholar : PubMed/NCBI
26	Zhao H, Mitchell S, Ciechanowicz S, Savage S, Wang T, Ji X and Ma D: Argon protects against hypoxic-ischemic brain injury in neonatal rats through activation of nuclear factor (erythroid-derived 2)-like 2. Oncotarget. 7:25640–25651. 2016.PubMed/NCBI
27	Zhai X, Lin H, Chen Y, Chen X, Shi J, Chen O, Li J and Sun X: Hyperbaric oxygen preconditioning ameliorates hypoxia-ischemia brain damage by activating Nrf2 expression in vivo and in vitro. Free Radic Res. 50:454–466. 2016. View Article : Google Scholar : PubMed/NCBI
28	Li B, Choi HJ, Lee DS, Oh H, Kim YC, Moon JY, Park WH, Park SD and Kim JE: Amomum tsao-ko suppresses lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages via Nrf2-dependent heme oxygenase-1 expression. Am J Chin Med. 42:1229–1244. 2014. View Article : Google Scholar : PubMed/NCBI
29	Yang H, Xu W, Zhou Z, Liu J, Li X, Chen L, Weng J and Yu Z: Curcumin attenuates urinary excretion of albumin in type II diabetic patients with enhancing nuclear factor erythroid-derived 2-like 2 (Nrf2) system and repressing inflammatory signaling efficacies. Exp Clin Endocrinol Diabetes. 123:360–367. 2015. View Article : Google Scholar : PubMed/NCBI
30	Rzepecka J, Pineda MA, Al-Riyami L, Rodgers DT, Huggan JK, Lumb FE, Khalaf AI, Meakin PJ, Corbet M, Ashford ML, et al: Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic worm product prevents experimental arthritis and inhibits IL-1β production via NRF2-mediated counter-regulation of the inflammasome. J Autoimmun. 60:59–73. 2015. View Article : Google Scholar : PubMed/NCBI
31	Zhang X, Liang D, Guo L, Liang W, Jiang Y, Li H, Zhao Y, Lu S and Chi ZH: Curcumin protects renal tubular epithelial cells from high glucose-induced epithelial-to-mesenchymal transition through Nrf2-mediated upregulation of heme oxygenase-1. Mol Med Rep. 12:1347–1355. 2015.PubMed/NCBI
32	Zimmermann K, Baldinger J, Mayerhofer B, Atanasov AG, Dirsch VM and Heiss EH: Activated AMPK boosts the Nrf2/HO-1 signaling axis-A role for the unfolded protein response. Free Radic Biol Med. 88:417–426. 2015. View Article : Google Scholar : PubMed/NCBI
33	Askalan R, Gabarin N, Armstrong EA, Liu Y Fang, Couchman D and Yager JY: Mechanisms of neurodegeneration after severe hypoxic-ischemic injury in the neonatal rat brain. Brain Res. 1629:94–103. 2015. View Article : Google Scholar : PubMed/NCBI
34	Cai J, Kang Z, Liu WW, Luo X, Qiang S, Zhang JH, Ohta S, Sun X, Xu W, Tao H and Li R: Hydrogen therapy reduces apoptosis in neonatal hypoxia-ischemia rat model. Neurosci Lett. 441:167–172. 2008. View Article : Google Scholar : PubMed/NCBI
35	Bucak A, Ozdemir C, Ulu S, Gonul Y, Aycicek A, Uysal M and Cangal A: Investigation of protective role of curcumin against paclitaxel-induced inner ear damage in rats. Laryngoscope. 125:1175–1182. 2015. View Article : Google Scholar : PubMed/NCBI