Advertisement
Research Article| Volume 268, P308-317, December 2021

Download started.

Ok

Perillaldehyde Alleviates Spinal Cord Ischemia-Reperfusion Injury Via Activating the Nrf2 Pathway

  • Wenjun Zheng
    Affiliations
    Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China

    Department of Cardiac Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
    Search for articles by this author
  • Bing Liu
    Affiliations
    Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China

    Department of Vascular Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
    Search for articles by this author
  • Enyi Shi
    Correspondence
    Corresponding author. E. Shi, Department of Cardiac Surgery, The First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning 110001, People's Republic of China. Tel.: +86-24-83283455.
    Affiliations
    Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China
    Search for articles by this author
Published:August 13, 2021DOI:https://doi.org/10.1016/j.jss.2021.06.055

      ABSTRACT

      Background

      Spinal Cord ischemia-reperfusion injury (SCII) is one of the most destructive complications in thoracic-abdominal aortic surgery, which can cause physical abnormalities, paralysis and even brain death. Evidence has shown that perillaldehyde (PAH) can ameliorate rat's cerebra ischemia-reperfusion injury. However, the effect of PAH on SCII remains unknown.

      Methods

      The current study established SCII rat models and oxygen and glucose deprivation/reoxygenation-induced BV2 microglia models to explore whether PAH could alleviate SCII symptoms and to investigate underlying mechanism.

      Results

      SCII rats underwent severe neurologic motor dysfunction and histopathologic injury compared with the normal rats, which are exhibited by loss of motor neurons and decrease of nissl bodies. Treatment with PAH significantly ameliorated motor dysfunction and neuron damage. PAH downregulated the expression of NLR family pyrin domain containing 3, cleaved/pro caspase-1, interleukin-1β and interleukin-18 in spinal cord tissues of SCII rats. Besides, the contents of oxidative stress-related factors superoxide dismutase, manganese-dependent superoxide dismutase, catalase and glutathione peroxidase were significantly increased and malondialdehyde content was decreased after PAH treatment. PAH treatment upregulated the expression of nuclear factor-E2-related factor 2 and heme oxygenase-1 in spinal cord tissues of SCII rats. Our in vitro study confirmed that PAH inhibited microglial activation by activating the nuclear factor-E2-related factor 2/heme oxygenase-1 pathway, exhibited by alleviated inflammation and oxidative stress.

      Conclusions

      This study elucidates that PAH has the potential value for treating SCII, which provides an experimental basis for clinical trials in the future.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Surgical Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Miranda V
        • Sousa J
        • Mansilha A
        • et al.
        Spinal cord injury in endovascular thoracoabdominal aortic aneurysm repair: prevalence, risk factors and preventive strategies.
        Int Angiol. 2018; 37: 112-126
        • Oruckaptan HH
        • Ozisik P
        • Atilla P
        • Tuncel M
        • Kilinc K
        • Geyik PO
        • et al.
        Systemic administration of interleukin-10 attenuates early ischemic response following spinal cord ischemia reperfusion injury in rats.
        J Surg Res. 2009; 155: 345-356
        • Okita Y
        Fighting spinal cord complication during surgery for thoracoabdominal aortic disease.
        Gen Thorac Cardiovasc Surg. 2011; 59: 79-90
        • Akhtar AM
        • Al Shehabi TS
        • Eid AH
        Inflammogenesis of Secondary Spinal Cord Injury.
        Front Cell Neurosci. 2016; 10: 98
        • Smith PD
        • Bell MT
        • Puskas F
        • Meng X
        • Cleveland JC Jr
        • Weyant MJ
        • et al.
        Preservation of motor function after spinal cord ischemia and reperfusion injury through microglial inhibition.
        Ann Thorac Surg. 2013; 95: 1647-1653
        • Li XQ
        • Cao XZ
        • Wang J
        • Fang B
        • Tan WF
        • Ma H
        Sevoflurane preconditioning ameliorates neuronal deficits by inhibiting microglial MMP-9 expression after spinal cord ischemia/reperfusion in rats.
        Mol Brain. 2014; 7: 69
        • Na HST
        • Nuo M
        • Meng QT
        • Xia ZY
        The pathway of let-7a-1/2-3p and HMGB1 mediated dexmedetomidine inhibiting microglia activation in spinal cord ischemia-reperfusion injury mice.
        J Mol Neurosci. 2019; 69: 106-114
        • Gęgotek A
        • Skrzydlewska E
        The role of transcription factor Nrf2 in skin cells metabolism.
        Arch Dermatol Res. 2015; 307: 385-396
        • Melba C.
        • Jaramillo MC
        • Zhang DD
        The emerging role of the Nrf2-Keap1 signaling pathway in cancer.
        Genes Dev. 2013; 27: 2179-2191
        • Kovac S
        • Angelova PR
        • Holmström KM
        • Zhang Y
        • Dinkova-Kostova AT
        • Abramov AY
        Nrf2 regulates ROS production by mitochondria and NADPH oxidase.
        Biochim Biophys Acta. 2015; 1850: 794-801
        • Zhang JY
        • Ohta T
        • Maruyama A
        • Hosoya T
        • Nishikawa K
        • Maher JM
        • et al.
        BRG1 interacts with Nrf2 to selectively mediate HO-1 induction in response to oxidative stress.
        Mol Cell Biol. 2006; 26: 7942-7952
        • Sies H
        Oxidative stress: a concept in redox biology and medicine.
        Redox Biol. 2015; 4: 180-183
        • Tsikas D
        Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: analytical and biological challenges.
        Anal Biochem. 2016; 524: 13-30
        • Gao L
        • Dong Q
        • Song ZH
        • Shen F
        • Shi J
        • Li Y
        NLRP3 inflammasome: a promising target in ischemic stroke.
        Inflamm Res. 2017; 66: 17-24
        • Rubartelli A
        Redox control of NLRP3 inflammasome activation in health and disease.
        J Leukoc Biol. 2012; 92: 951-958
        • Minutoli L
        • Puzzolo D
        • Rinaldi M
        • Irrera N
        • Marini H
        • Arcoraci V
        • et al.
        ROS-mediated NLRP3 inflammasome activation in brain, heart, kidney, and testis ischemia/reperfusion injury.
        Oxid Med Cell Longev. 2016; 20162183026
        • Xu XJ
        • Zhang L
        • Ye XC
        • Hao T
        • Zhang T
        • Cui GY
        • et al.
        Nrf2/ARE pathway inhibits ROS-induced NLRP3 inflammasome activation in BV2 cells after cerebral ischemia reperfusion.
        Inflamm Res. 2018; 67: 57-65
        • Fuyuno Y
        • Uchi H
        • Yasumatsu M
        • Morino-Koga S
        • Tanaka Y
        • Mitoma C
        • et al.
        Perillaldehyde inhibits AHR signaling and activates NRF2 antioxidant pathway in human keratinocytes.
        Oxid Med Cell Longev. 2018; 2018: 1-9
        • Li Y
        • Yu L
        • Liu H
        Perillaldehyde prevents the formations of atherosclerotic plaques through recoupling endothelial nitric oxide synthase.
        J Cell Biochem. 2018; 119: 10204-10215
        • Tian J
        • Wang YZ
        • Lu ZQ
        • Sun CH
        • Zhang M
        • Zhu AH
        • et al.
        Perillaldehyde, a promising antifungal agent used in food preservation, triggers apoptosis through a metacaspase-dependent pathway in aspergillus flavus.
        J Agric Food Chem. 2016; 64: 7404-7413
        • Xu LX
        • Li YB
        • Fu Q
        • Ma S
        Perillaldehyde attenuates cerebral ischemia-reperfusion injury-triggered overexpression of inflammatory cytokines via modulating Akt/JNK pathway in the rat brain cortex.
        Biochem Biophys Res Commun. 2014; 454: 65-70
        • Gokce EC
        • Kahveci R
        • Gokce A
        • Sargon MF
        • Kisa U
        • Aksoy N
        • et al.
        Curcumin attenuates inflammation, oxidative stress, and ultrastructural damage induced by spinal cord ischemia-reperfusion injury in rats.
        J Stroke Cerebrovasc Dis. 2016; 25: 1196-1207
        • Basso DM
        • Beattie MS
        • Bresnahan JC
        • Anderson DK
        • Faden AI
        • Gruner JA
        • et al.
        MASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Multicenter animal spinal cord injury study.
        J Neurotrauma. 1996; 13: 343-359
        • Yin F
        • Guo L
        • Meng CY
        • Liu YJ
        • Lu RF
        • Li P
        • et al.
        Transplantation of mesenchymal stem cells exerts anti-apoptotic effects in adult rats after spinal cord ischemia-reperfusion injury.
        Brain Res. 2014; 1561: 1-10
        • Dolunay A
        • Senol SP
        • Temiz-Resitoglu M
        • Guden DS
        • Sari AN
        • Sahan-Firat S
        • et al.
        Inhibition of NLRP3 inflammasome prevents LPS-induced inflammatory hyperalgesia in mice: contribution of NF-κB, Caspase-1/11, ASC, NOX, and NOS isoforms.
        Inflammation. 2017; 40: 366-386
        • He Q
        • Li Z
        • Wang Y
        • Li LY
        • Zhao J
        Resveratrol alleviates cerebral ischemia/reperfusion injury in rats by inhibiting NLRP3 inflammasome activation through Sirt1-dependent autophagy induction.
        Int Immunopharmacol. 2017; 50: 208-215
        • Masutani H
        • Otsuki R
        • Yamaguchi Y
        • Takenaka M
        • Kanoh N
        • Takatera K
        • et al.
        Fragrant unsaturated aldehydes elicit activation of the Keap1/Nrf2 system leading to the upregulation of thioredoxin expression and protection against oxidative stress.
        Antioxid Redox Signal. 2009; 11: 949-962
        • Du XL
        • Shi Z
        • Peng ZC
        • Zhao CX
        • Zhang YM
        • Wang Z
        • et al.
        Acetoacetate induces hepatocytes apoptosis by the ROS-mediated MAPKs pathway in ketotic cows.
        J Cell Physiol. 2017; 232: 3296-3308
        • Li W
        • Khor TO
        • Xu CJ
        • Shen GX
        • Jeong WS
        • Yu SW
        • et al.
        Activation of Nrf2-antioxidant signaling attenuates NFκB-inflammatory response and elicits apoptosis.
        Biochem Pharmacol. 2008; 76: 1485-1489
        • Ystgaard MB
        • Sejersted Y
        • Løberg EM
        • Lien E
        • Yndestad A
        • Saugstad OD
        Early upregulation of NLRP3 in the brain of neonatal mice exposed to hypoxia-ischemia: no early neuroprotective effects of NLRP3 deficiency.
        Neonatology. 2015; 108: 211-219
        • Satoh T
        • Kambe N
        • Matsue H
        NLRP3 activation induces ASC-dependent programmed necrotic cell death, which leads to neutrophilic inflammation.
        Cell Death Dis. 2013; 4 (e644-e644)