Skip to main content
SpringerLink
Log in

Syringic acid ameliorates ischemia/reperfusion-induced testicular injury in rats via suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress

  • Original Article
  • Published:
European Journal of Trauma and Emergency Surgery Aims and scope Submit manuscript

Abstract

Purpose

To investigate the possible protective role of syringic acid on torsion/detorsion-induced testicular injury using biochemical and histopathological approaches for the first time.

Methods

A total of 24 rats were divided into 4 groups: sham control, torsion/detorsion, torsion/detorsion + syringic acid (50 mg/kg and 100 mg/kg). Tissue malondialdehyde, total oxidant status and total antioxidant status levels were determined using colorimetric methods. Tissue 8-hydroxy-2′-deoxyguanosine, superoxide dismutase, catalase, high mobility group box 1, nuclear factor kappa B protein 65, tumor necrosis factor-alpha, interleukin-6, myeloperoxidase, 78-kDa glucose-regulated protein, activating transcription factor-6, C/EBP homologous protein and caspase-3 levels were determined using commercial enzyme-linked immunosorbent assay kits. Johnsen’s testicle scoring system was used for histological evaluation.

Results

Compared with the control group, the levels of oxidative stress, inflammation, endoplasmic reticulum stress and apoptosis were significantly increased in the torsion/detorsion group (p < 0.05). Syringic acid administrations statistically significantly restored these damage in a dose dependent manner (p < 0.05). Moreover, it was found that the results of histological examinations supported the biochemical results to a statistically significant extent.

Conclusion

The overall results suggest that syringic acid emerges as a potential compound for the treatment of testicular torsion and may be subject to clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

The data presented in the current study are available from the corresponding author on reasonable request.

Abbreviations

8-OHdG:

8-Hydroxy-2′-deoxyguanosine

ATF6:

Activating transcription factor 6

CAT:

Catalase

CHOP:

C/EBP homologous protein

DMSO:

Dimethyl sulfoxide

ELISA:

Enzyme-linked immunosorbent assay

ER:

Endoplasmic reticulum

ERAD:

Endoplasmic reticulum-associated degradation

GPx:

Glutathione peroxidase

GRP78:

78-KDa glucose-regulated protein

H&E:

Hematoxylin and eosin

HMGB1:

High mobility group box 1

IP:

Intraperitoneal

I/R:

Ischemia/reperfusion

IL-6:

Interleukin-6

IRE1:

Inositol requiring enzyme 1

IRI:

Ischemia/reperfusion injury

IQR:

Interquantile range

MDA:

Malondialdehyde

MPO:

Myeloperoxidase

NF-κB p65:

Nuclear factor kappa B protein 65

OSI:

Oxidative stress index

PBS:

Phosphate buffered saline

PERK:

Protein kinase RNA-activated-like ER kinase

ROS:

Reactive oxygen species

SA:

Syringic acid

SOD:

Superoxide dismutase

TAS:

Total antioxidant status

TBA:

Thiobarbituric acid

T/D:

Torsion/detorsion

TNF-α:

Tumor necrosis factor-alpha

TOS:

Total oxidant status

TT:

Testicular torsion

UPR:

Unfolded protein response

References

  1. Vaos G, Zavras N. Antioxidants in experimental ischemia-reperfusion injury of the testis: Where are we heading towards? World J Methodol. 2017;7(2):37–45.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Shunmugam M, Goldman RD. Testicular torsion in children. Can Fam Physician. 2021;67(9):669–71.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Unsal V, Kolukcu E, Gevrek F, Firat F. Sinapic acid reduces ischemia/reperfusion injury due to testicular torsion/detorsion in rats. Andrologia. 2021;53(8): e14117.

    Article  CAS  PubMed  Google Scholar 

  4. Sancak EB, Akbas A, Silan C, Cakir DU, Turkon H, Ozkanli SS. Protective effect of syringic acid on kidney ischemia-reperfusion injury. Ren Fail. 2016;38(4):629–35.

    Article  CAS  PubMed  Google Scholar 

  5. Karaguzel E, Kadihasanoglu M, Kutlu O. Mechanisms of testicular torsion and potential protective agents. Nat Rev Urol. 2014;11:391–9.

    Article  CAS  PubMed  Google Scholar 

  6. Li Y, Zhang L, Wang X, Wu W, Qin R. Effect of syringic acid on antioxidant biomarkers and associated inflammatory markers in mice model of asthma. Drug Dev Res. 2019;80(2):253–61.

    Article  CAS  PubMed  Google Scholar 

  7. Srinivasulu C, Ramgopal M, Ramanjaneyulu G, Anuradha CM, Kumar CS. Syringic acid (SA)-A review of its occurrence, biosynthesis, pharmacological and industrial importance. Biomed Pharmacother. 2018;108:547–57.

    Article  CAS  PubMed  Google Scholar 

  8. Reyes-Fermín LM, Aparicio-Trejo OE, Avila-Rojas SH, Gómez-Sierra T, Martínez-Klimova E, Pedraza-Chaverri J. Natural antioxidants’ effects on endoplasmic reticulum stress-related diseases. Food Chem Toxicol. 2020;138: 111229.

    Article  PubMed  Google Scholar 

  9. Martucciello S, Masullo M, Cerulli A, Piacente S. Natural products targeting ER stress, and the functional link to mitochondria. Int J Mol Sci. 2020;21:1905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tungalag T, Yang DK. Sinapic acid protects SH-SY5Y human neuroblastoma cells against 6-hydroxydopamine-induced neurotoxicity. Biomedicines. 2021;9(3):295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Güven M, Aras AB, Topaloğlu N, Özkan A, Şen HM, Kalkan Y, Okuyucu A, Akbal A, Gökmen F, Coşar M. The protective effect of syringic acid on ischemia injury in rat brain. Turk J Med Sci. 2015;45(1):233–40.

    Article  PubMed  Google Scholar 

  12. Liu G, Zhang BF, Hu Q, Liu XP, Chen J. Syringic acid mitigates myocardial ischemia reperfusion injury by activating the PI3K/Akt/GSK-3β signaling pathway. Biochem Biophys Res Commun. 2020;531(2):242–9.

    Article  CAS  PubMed  Google Scholar 

  13. Turner TT, Tung KS, Tomomasa H, Wilson LW. Acute testicular ischemia results in germ cell-specific apoptosis in the rat. Biol Reprod. 1997;57(6):1267–74.

    Article  CAS  PubMed  Google Scholar 

  14. Demir S, Kazaz IO, Kerimoglu G, Demir EA, Colak F, Yilmaz S, Mentese A. Astaxanthin protects testicular tissue against torsion/detorsion-induced injury via suppressing endoplasmic reticulum stress in rats. J Invest Surg. 2022;35(5):1044–9.

    Article  PubMed  Google Scholar 

  15. Kazaz IO, Demir S, Kerimoglu G, Colak F, Alemdar NT, Dogan SY, Bostan S, Mentese A. Chlorogenic acid ameliorates torsion/detorsion-induced testicular injury via decreasing endoplasmic reticulum stress. J Pediatr Urol. 2022;18(3):289.e1-e7.

    Article  PubMed  Google Scholar 

  16. Manjunatha S, Shaik AH, Prasad EM, Omar SYA, Mohammad A, Kodidhela LD. Combined cardio-protective ability of syringic acid and resveratrol against isoproterenol induced cardio-toxicity in rats via attenuating NF-kB and TNF-α pathways. Sci Rep. 2020;10(1):3426.

    Article  CAS  Google Scholar 

  17. Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978;86(1):271–8.

    Article  CAS  PubMed  Google Scholar 

  18. Demir EA, Mentese A, Kucuk H, Alemdar NT, Demir S. p-Coumaric acid alleviates cisplatin-induced ovarian toxicity in rats. J Obstet Gynaecol Res. 2022;48(2):411–9.

    Article  PubMed  Google Scholar 

  19. Johnsen SG. Testicular biopsy score count-A method for registration of spermatogenesis in human testes: Normal values and results in 335 hypogonadal males. Hormones. 1970;1:2–25.

    CAS  PubMed  Google Scholar 

  20. Shahzad S, Mateen S, Kausar T, Naeem SS, Hasan A, Abidi M, Nayeem SM, Faizy AF, Moin S. Effect of syringic acid and syringaldehyde on oxidative stress and inflammatory status in peripheral blood mononuclear cells from patients of myocardial infarction. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(4):691–704.

    Article  CAS  PubMed  Google Scholar 

  21. Ye Y, Zeng Z, Jin T, Zhang H, Xiong X, Gu L. The role of high mobility group box 1 in ischemic stroke. Front Cell Neurosci. 2019;13:127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhang B, Zhong Q, Chen X, Wu X, Sha R, Song G, Zhang C, Chen X. Neuroprotective effects of celastrol on transient global cerebral ischemia rats via regulating HMGB1/NF-κB signaling pathway. Front Neurosci. 2020;14:847.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kim IH, Yan BC, Park JH, Yeun GH, Yim Y, Ahn JH, Lee JC, Hwang IK, Cho JH, Kim YM, Lee YL, Park JH, Won MH. Neuroprotection of a novel synthetic caffeic acid-syringic acid hybrid compound against experimentally induced transient cerebral ischemic damage. Planta Med. 2013;79(5):313–21.

    Article  CAS  PubMed  Google Scholar 

  24. Lin CL. Attenuation of endoplasmic reticulum stress as a treatment strategy against ischemia/reperfusion injury. Neural Regen Res. 2015;10(12):1930–1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Xin Q, Ji B, Cheng B, Wang C, Liu H, Chen X, Chen J, Bai B. Endoplasmic reticulum stress in cerebral ischemia. Neurochem Int. 2014;68:18–27.

    Article  CAS  PubMed  Google Scholar 

  26. Li X, Zhang X, Xing R, Qi F, Dong J, Li D, Yu B, Huang M, Zhang L, Yuan X, Yang Y, Wu H, Zang L, Mao X, Sui R. Syringic acid demonstrates promising protective effect against tau fibrillization and cytotoxicity through regulation of endoplasmic reticulum stress-mediated pathway as a prelude to Alzheimer’s disease. Int J Biol Macromol. 2021;192:491–7.

    Article  CAS  PubMed  Google Scholar 

  27. Kazaz IO, Demir S, Kerimoglu G, Colak F, Alemdar NT, Akman AU, Cekuc OC, Mentese A. Effect of chrysin on endoplasmic reticulum stress in a rat model of testicular torsion. J Invest Surg. 2022;35(5):1106–11.

    Article  PubMed  Google Scholar 

  28. Demir S, Kazaz IO, Aliyazicioglu Y, Kerimoglu G, Teoman AS, Yaman SO, Arslan A, Mentese A. Effect of ethyl pyruvate on oxidative state and endoplasmic reticulum stress in a rat model of testicular torsion. Biotech Histochem. 2020;95(4):317–22.

    Article  CAS  PubMed  Google Scholar 

  29. Cikman O, Soylemez O, Ozkan OF, Kiraz HA, Sayar I, Ademoglu S, Taysi S, Karaayvaz M. Antioxidant activity of syringic acid prevents oxidative stress in L-arginine-induced acute pancreatitis: An experimental study on rats. Int Surg. 2015;100:891–6.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Chemistry and Chemical Processing Technologies, Macka Vocational School, Karadeniz Technical University, 61750, Trabzon, Turkey

    Elif Ayazoglu Demir

  2. Department of Nutrition and Dietetics, Faculty of Health Sciences, Karadeniz Technical University, 61080, Trabzon, Turkey

    Selim Demir

  3. Department of Urology, Faculty of Medicine, Karadeniz Technical University, 61080, Trabzon, Turkey

    Ilke Onur Kazaz & Omer Faruk Gecici

  4. Department of Pathology, Trabzon Kanuni Training and Research Hospital, University of Health Sciences, 61250, Trabzon, Turkey

    Hatice Kucuk

  5. Department of Medical Biochemistry, Graduate School of Health Sciences, Karadeniz Technical University, 61080, Trabzon, Turkey

    Nihal Turkmen Alemdar

  6. Department of Medical Services and Techniques, Vocational School of Health Services, Recep Tayyip Erdogan University, 53100, Rize, Turkey

    Nihal Turkmen Alemdar

  7. Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, 61080, Trabzon, Turkey

    Ahmet Mentese & Yuksel Aliyazicioglu

Authors
  1. Elif Ayazoglu Demir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Selim Demir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ilke Onur Kazaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hatice Kucuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nihal Turkmen Alemdar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Omer Faruk Gecici
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ahmet Mentese
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yuksel Aliyazicioglu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

EAD: Conceptualization, data curation, validation, investigation, software, writing-original draft. SD: Conceptualization, methodology, formal analysis, writing-original draft. IOK: Conceptualization, methodology and writing-original draft. HK: Methodology, investigation. NTA: Methodology, Formal analysis. OFG: Methodology. AM: Data curation, validation, investigation, software. YA: Investigation, writing-original draft.

Corresponding author

Correspondence to Selim Demir.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

This study was approved by the Experimental Animal Local Ethics Committee of Karadeniz Technical University (Protocol no: 2021/65) and performed according to the animal research reporting of in vivo experiments (ARRIVE) guidelines.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Demir, E.A., Demir, S., Kazaz, I.O. et al. Syringic acid ameliorates ischemia/reperfusion-induced testicular injury in rats via suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress. Eur J Trauma Emerg Surg 49, 1595–1602 (2023). https://doi.org/10.1007/s00068-023-02227-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00068-023-02227-7

Keywords

Search

Navigation