Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
May-2016 Volume 13 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2016 Volume 13 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Protective effect of berberine on doxorubicin‑induced acute hepatorenal toxicity in rats

  • Authors:
    • Xueyan Chen
    • Yu Zhang
    • Zhongning Zhu
    • Huanlong Liu
    • Huicai Guo
    • Chen Xiong
    • Kerang Xie
    • Xiaofei Zhang
    • Suwen Su
  • View Affiliations / Copyright

    Affiliations: The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, The Family Planning Research Institute of Hebei, Shijiazhuang, Hebei 050000, P.R. China, Pharmaceutical Department, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
  • Pages: 3953-3960
    |
    Published online on: March 21, 2016
       https://doi.org/10.3892/mmr.2016.5017
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Doxorubicin (DOX), a potent broad‑spectrum chemotherapeutic agent used for the treatment of several types of cancer, is largely limited due to its serious side effects on non‑target organs. Thus, the present study aimed to investigate whether berberine (Ber), an isoquinoline alkaloid, could reduce DOX‑induced acute hepatorenal toxicity in rats. Fifty rats were randomly divided into five groups: i) Control group, ii) DOX group, iii) DOX+Ber (5 mg kg) group; iv) DOX+Ber (10 mg kg), and v) DOX+Ber (20 mg kg) group. In the tests, body weight, organ index, general condition and mortality were observed. In addition, the serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TCHO) and blood urea nitrogen (BUN) were determined to evaluate hepatorenal function. Hepatorenal toxicity was further assessed using hematoxylin and eosin stained sections. Furthermore, the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) in rat serum or tissue homogenate were also assessed to determine the mechanisms of action. Results suggested that pretreatment with Ber ameliorated the DOX‑induced liver and kidney injury by lowering the serum ALT, AST, TCHO and BUN levels, and the damage observed histologically, such as hemorrhage and focal necrosis of liver and kidney tissues induced by DOX were also attenuated by Ber. Furthermore, Ber also exerted certain antioxidative properties through reversing the changes in the levels of MDA, SOD, GSH and MDA induced by DOX. These findings indicate that Ber has protective effects against DOX‑induced acute hepatorenal toxicity in rats. Combination of Ber with DOX is a novel strategy that has the potential for protecting against DOX‑induced hepatorenal toxicity in clinical practice.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Cheng C, Xue W, Diao H, Xia S, Zuo L, He A, Gao F, Huang Z, Chen J and Zhang J: Antitumor activity and toxicological properties of doxorubicin conjugated to [alpha], [beta]-poly [(2-hydroxyethyl)-L-aspartamide] administered intraperitoneally in mice. Anticancer Drugs. 21:362–371. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Tangpong J, Miriyala S, Noel T, Sinthupibulyakit C, Jungsuwadee P and St Clair DK: Doxorubicin-induced central nervous system toxicity and protection by xanthone derivative of Garcinia mangostana. Neuroscience. 175:292–299. 2011. View Article : Google Scholar :

3 

Cardoso S, Santos RX, Carvalho C, Correia S, Pereira GC, Pereira SS, Oliveira PJ, Santos MS, Proença T and Moreira PI: Doxorubicin increases the susceptibility of brain mitochondria to Ca(2+)-induced permeability transition and oxidative damage. Free Radic Biol Med. 45:1395–1402. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Kalender Y, Yel M and Kalender S: Doxorubicin hepatotoxicity and hepatic free radical metabolism in rats. The effects of vitamin E and catechin. Toxicology. 209:39–45. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Bárdi E, Bobok I, Voláh A, Kappelmayer J and Kiss C: Anthracycline antibiotics induce acute renal tubular toxicity in children with cancer. Pathol Oncol Res. 13:249–253. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Yang XL, Fan CH and Zhu HS: Photo-induced cytotoxicity of malonic acid [C(60)]fullerene derivatives and its mechanism. Toxicol In Vitro. 16:41–46. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Badkoobeh P, Parivar K, Kalantar SM, Hosseini SD and Salabat A: Effect of nano-zinc oxide on doxorubicin-induced oxidative stress and sperm disorders in adult male Wistar rats. Iran J Reprod Med. 11:355–364. 2013.

8 

Li L, Takemura G, Li Y, Miyata S, Esaki M, Okada H, Kanamori H, Khai NC, Maruyama R, Ogino A, et al: Preventive effect of erythropoietin on cardiac dysfunction in doxorubicin-induced cardiomyopathy. Circulation. 113:535–543. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Yeh YC, Lai HC, Ting CT, Lee WL, Wang LC, Wang KY, Lai HC and Liu TJ: Protection by doxycycline against doxorubicin-induced oxidative stress and apoptosis in mouse testes. Biochem Pharmacol. 74:969–980. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Tang LQ, Wang FL, Zhu LN, Lv F, Liu S and Zhang ST: Berberine ameliorates renal injury by regulating G proteins-AC- cAMP signaling in diabetic rats with nephropathy. Mol Biol Rep. 40:3913–3923. 2013. View Article : Google Scholar

11 

Wang Y, Huang Y, Lam KS, Li Y, Wong WT, Ye H, Lau CW, Vanhoutte PM and Xu A: Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase. Cardiovasc Res. 82:484–492. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Derosa G, Maffioli P and Cicero AF: Berberine on metabolic and cardiovascular risk factors: An analysis from preclinical evidences to clinical trials. Expert Opin Biol Ther. 12:1113–1124. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Cho BJ, Im EK, Kwon JH, Lee KH, Shin HJ, Oh J, Kang SM, Chung JH and Jang Y: Berberine inhibits the production of lysophosphatidylcholine-induced reactive oxygen species and the ERK1 2 pathway in vascular smooth muscle cells. Mol Cells. 20:429–434. 2005.

14 

Li J, Pan Y, Kan M, Xiao X, Wang Y, Guan F, Zhang X and Chen L: Hepatoprotective effects of berberine on liver fibrosis via activation of AMP-activated protein kinase. Life Sci. 98:24–30. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Hsu YY, Tseng YT and Lo YC: Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth. Toxicol Appl Pharmacol. 272:787–796. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Marin-Neto JA, Maciel BC, Secches AL and Gallo Junior L: Cardiovascular effects of berberine in patients with severe congestive heart failure. Clin Cardiol. 11:253–260. 1988. View Article : Google Scholar : PubMed/NCBI

17 

Zhao X, Zhang J, Tong N, Liao X, Wang E, Li Z, Luo Y and Zuo H: Berberine attenuates doxorubicin-induced cardiotoxicity in mice. J Int Med Res. 39:1720–1727. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Kelishomi RB, Ejtemaeemehr S, Tavangar SM, Rahimian R, Mobarakeh JI and Dehpour AR: Morphine is protective against doxorubicin-induced cardiotoxicity in rat. Toxicology. 243:96–104. 2008. View Article : Google Scholar

19 

Jing L, Wu Y, Wu J, Zhao J, Zuo D and Peng S: Peroxiredoxins are involved in metallothionein protection from doxorubicin cardiotoxicity. Eur J Pharmacol. 659:224–232. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Hou XW, Jiang Y, Wang LF, Xu HY, Lin HM, He XY, He JJ and Zhang S: Protective role of granulocyte colony-stimulating factor against adriamycin induced cardiac, renal and hepatic toxicities. Toxicol Lett. 187:40–44. 2009. View Article : Google Scholar : PubMed/NCBI

21 

You JS, Pan TL and Lee YS: Protective effects of Danshen (Salvia miltiorrhiza) on adriamycin-induced cardiac and hepatic toxicity in rats. Phytother Res. 21:1146–1152. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Outomuro D, Grana DR, Azzato F and Milei J: Adriamycin-induced myocardial toxicity: New solutions for an ole problems? Int J Cardiol. 117:6–15. 2007. View Article : Google Scholar

23 

Piscitelli SC, Rodvold KA, Rushing DA and Tewksbury DA: Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small-cell lung cancer. Clin Pharmacol Ther. 53:555–561. 1993. View Article : Google Scholar : PubMed/NCBI

24 

Swain SM, Whaley FS and Ewer MS: Congestive heart failure in patients treated with doxorubicin: A retrospective analysis of three trials. Cancer. 97:2869–2879. 2003. View Article : Google Scholar : PubMed/NCBI

25 

King SL, Mohiuddin JJ and Dekaney CM: Paneth cells expand from newly created and preexisting cells during repair after doxorubicin-induced damage. Am J Physiol Gastrointest Liver Physiol. 305:G151–G162. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Tong N, Zhang J, Chen Y, Li Z, Luo Y, Zuo H and Zhao X: Berberine sensitizes mutliple human cancer cells to the anticancer effects of doxorubicin in vitro. Oncol Lett. 3:1263–1267. 2012.PubMed/NCBI

27 

Abd El-Wahab AE, Ghareeb DA, Sarhan EE, Abu-Serie MM and El Demellawy MA: In vitro biological assessment of Berberis vulgaris and its active constituent, berberine: Antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effects. BMC Complement Altern Med. 13:2182013. View Article : Google Scholar : PubMed/NCBI

28 

Yan K, Zhang C, Feng J, Hou L, Yan L, Zhou Z, Liu Z, Liu C, Fan Y, Zheng B and Xu Z: Induction of G1 cell cycle arrest and apoptosis by berberine in bladder cancer cells. Eur J Pharmacol. 661:1–7. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Youn MJ, So HS, Cho HJ, Kim HJ, Kim Y, Lee JH, Sohn JS, Kim YK, Chung SY and Park R: Berberine, a natural product, combined with cisplatin enhanced apoptosis through a mitochondria caspase-mediated pathway in HeLa cells. Biol Pharm Bull. 31:789–795. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Hsu YY, Chen CS, Wu SN, Jong YJ and Lo YC: Berberine activates Nrf2 nuclear translocation and protects against oxidative damage via a phosphatidylinositol 3-kinase Akt-dependent mechanism in NSC34 motor neuron-like cells. Eur J Pharm Sci. 46:415–425. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Lv XX, Yu XH, Wang HD, Yan YX, Wang YP, Lu DX, Qi RB, Hu CF and Li HM: Berberine inhibits norepinephrine-induced apoptosis in neonatal rat cardiomyocytes via inhibiting ROS-TNF-α-caspase signaling pathway. Chin J Integr Med. 19:424–431. 2013. View Article : Google Scholar

32 

Cheng F, Wang Y, Li J, Su C, Wu F, Xia WH, Yang Z, Yu BB, Qiu YX and Tao J: Berberine improves endothelial function by reducing endothelial microparticles-mediated oxidative stress in humans. Int J Cardiol. 167:936–942. 2013. View Article : Google Scholar

33 

Shen L and Ji HF: The mechanisms of ROS-photogeneration by berberine, a natural isoquinoline alkaloid. J Photochem Photobiol B. 99:154–156. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Zhao X, Zhang J, Tong N, Chen Y and Luo Y: Protective effects of berberine on doxorubicin-induced hepatotoxicity in mice. Biol Pharm Bull. 35:796–800. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen X, Zhang Y, Zhu Z, Liu H, Guo H, Xiong C, Xie K, Zhang X and Su S: Protective effect of berberine on doxorubicin‑induced acute hepatorenal toxicity in rats. Mol Med Rep 13: 3953-3960, 2016.
APA
Chen, X., Zhang, Y., Zhu, Z., Liu, H., Guo, H., Xiong, C. ... Su, S. (2016). Protective effect of berberine on doxorubicin‑induced acute hepatorenal toxicity in rats. Molecular Medicine Reports, 13, 3953-3960. https://doi.org/10.3892/mmr.2016.5017
MLA
Chen, X., Zhang, Y., Zhu, Z., Liu, H., Guo, H., Xiong, C., Xie, K., Zhang, X., Su, S."Protective effect of berberine on doxorubicin‑induced acute hepatorenal toxicity in rats". Molecular Medicine Reports 13.5 (2016): 3953-3960.
Chicago
Chen, X., Zhang, Y., Zhu, Z., Liu, H., Guo, H., Xiong, C., Xie, K., Zhang, X., Su, S."Protective effect of berberine on doxorubicin‑induced acute hepatorenal toxicity in rats". Molecular Medicine Reports 13, no. 5 (2016): 3953-3960. https://doi.org/10.3892/mmr.2016.5017
Copy and paste a formatted citation
x
Spandidos Publications style
Chen X, Zhang Y, Zhu Z, Liu H, Guo H, Xiong C, Xie K, Zhang X and Su S: Protective effect of berberine on doxorubicin‑induced acute hepatorenal toxicity in rats. Mol Med Rep 13: 3953-3960, 2016.
APA
Chen, X., Zhang, Y., Zhu, Z., Liu, H., Guo, H., Xiong, C. ... Su, S. (2016). Protective effect of berberine on doxorubicin‑induced acute hepatorenal toxicity in rats. Molecular Medicine Reports, 13, 3953-3960. https://doi.org/10.3892/mmr.2016.5017
MLA
Chen, X., Zhang, Y., Zhu, Z., Liu, H., Guo, H., Xiong, C., Xie, K., Zhang, X., Su, S."Protective effect of berberine on doxorubicin‑induced acute hepatorenal toxicity in rats". Molecular Medicine Reports 13.5 (2016): 3953-3960.
Chicago
Chen, X., Zhang, Y., Zhu, Z., Liu, H., Guo, H., Xiong, C., Xie, K., Zhang, X., Su, S."Protective effect of berberine on doxorubicin‑induced acute hepatorenal toxicity in rats". Molecular Medicine Reports 13, no. 5 (2016): 3953-3960. https://doi.org/10.3892/mmr.2016.5017
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team