Islet Transplantation Attenuating Testicular Injury in Type 1 Diabetic Rats Is Associated with Suppression of Oxidative Stress and Inflammation via Nrf-2/HO-1 and NF- κ B Pathways.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Hindawi Limited Country of Publication: England NLM ID: 101605237 Publication Model: eCollection Cited Medium: Internet ISSN: 2314-6753 (Electronic) NLM ISO Abbreviation: J Diabetes Res Subsets: MEDLINE
    • Publication Information:
      Publication: <2019>-: London, United Kingdom : Hindawi Limited
      Original Publication: Nasr City, Cairo : Hindawi Publishing Corporation, [2013]-
    • Subject Terms:
      Islets of Langerhans Transplantation*; Diabetes Complications/*surgery ; Diabetes Mellitus, Experimental/*surgery ; Inflammation/*metabolism ; Oxidative Stress/*physiology ; Signal Transduction/*physiology ; Testicular Diseases/*surgery ; Testis/*metabolism; Animals ; Diabetes Complications/drug therapy ; Diabetes Complications/metabolism ; Diabetes Complications/pathology ; Diabetes Mellitus, Experimental/drug therapy ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology ; Heme Oxygenase (Decyclizing)/metabolism ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/therapeutic use ; Inflammation/pathology ; Insulin/pharmacology ; Insulin/therapeutic use ; Male ; Malondialdehyde/metabolism ; NF-E2-Related Factor 2/metabolism ; NF-kappa B/metabolism ; Oxidative Stress/drug effects ; Rats ; Rats, Wistar ; Signal Transduction/drug effects ; Sperm Count ; Testicular Diseases/drug therapy ; Testicular Diseases/metabolism ; Testicular Diseases/pathology ; Testis/drug effects ; Testis/pathology
    • Abstract:
      Testicular structural and functional impairment is a serious complication in male diabetes mellitus (DM) patients that leads to impaired fertility in adulthood. In contrast to other endocrine therapies, islet transplantation (IT) can effectively prevent and even reverse diabetic nephropathy and myocardial damage. However, whether IT can alleviate diabetes-induced testicular injury remains unclear. In this study, we sought to investigate the effect of IT on diabetes-induced testicular damage. A diabetic rat model was established by streptozotocin injection. DM, IT, and insulin treatment (INS) groups were compared after 4 weeks of respective treatment. We confirmed that IT could effectively attenuate diabetes-induced testicular damage and recover sperm counts more extensively compared with INS in diabetic rats. In addition, significantly higher levels of superoxide dismutase (SOD) activity and lower contents of malondialdehyde (MDA) were detected in the testes of the IT group versus diabetic rats. Mechanism studies revealed that IT significantly activates the expression of Nrf-2, HO-1, and NQO-1 and inhibits upregulation of the NF- κ B expression in response to DM, while INS only exhibit slight impact on the protein expression. Therefore, we speculate that IT may prevent the progression of testicular damage by downregulating oxidative stress and inhibiting inflammation via Nrf-2/HO-1 and NF- κ B pathways.
      Competing Interests: All authors declare that there are no financial or nonfinancial competing interests regarding the publication of this paper.
      (Copyright © 2019 Xiandong Zhu et al.)
    • References:
      J Sex Med. 2009 May;6(5):1232-47. (PMID: 19210706)
      J Androl. 2009 Mar-Apr;30(2):190-9. (PMID: 18835830)
      Lancet. 2011 Jul 2;378(9785):31-40. (PMID: 21705069)
      EMBO J. 1991 Aug;10(8):2247-58. (PMID: 2065663)
      Andrology. 2015 May;3(3):450-61. (PMID: 25951427)
      J Ethnopharmacol. 2002 Oct;82(2-3):169-75. (PMID: 12241992)
      Mol Cell Biol. 2004 Apr;24(7):2593-604. (PMID: 15024051)
      Eur Cytokine Netw. 2005 Jun;16(2):161-5. (PMID: 15941688)
      Biol Pharm Bull. 2010;33(1):29-34. (PMID: 20045931)
      Curr Mol Med. 2019;19(1):12-19. (PMID: 30806316)
      Physiol Int. 2016 Dec;103(4):413-427. (PMID: 28229631)
      Sex Med Rev. 2017 Jan;5(1):45-51. (PMID: 27544297)
      Am J Physiol Endocrinol Metab. 2014 May 15;306(10):E1217-24. (PMID: 24691031)
      Diabetes. 2016 Sep;65(9):2700-10. (PMID: 27284112)
      Eur Surg Res. 1990;22(5):270-8. (PMID: 2079089)
      Andrologia. 2012 May;44 Suppl 1:654-60. (PMID: 22050043)
      Reprod Toxicol. 2014 Jan;43:30-7. (PMID: 24184564)
      Hum Reprod. 2002 Oct;17(10):2673-7. (PMID: 12351547)
      Br Med Bull. 1993 Jul;49(3):642-52. (PMID: 8221029)
      Diabetologia. 2009 Dec;52(12):2653-61. (PMID: 19789851)
      Arch Ital Urol Androl. 2017 Oct 03;89(3):212-218. (PMID: 28969406)
      Cell Transplant. 2003;12(1):33-41. (PMID: 12693662)
      Nat Rev Urol. 2012 May 01;9(6):330-8. (PMID: 22549313)
      Eur J Pharmacol. 2016 Nov 15;791:8-24. (PMID: 27568833)
      Clin Chem. 1997 Jul;43(7):1209-14. (PMID: 9216458)
      Hum Reprod Update. 2018 Jan 1;24(1):86-105. (PMID: 29136166)
      Cell Mol Life Sci. 2013 Mar;70(5):777-93. (PMID: 23011766)
      Diabetes. 1990 Nov;39(11):1420-4. (PMID: 2227114)
      Endocr J. 2017 Sep 30;64(9):907-922. (PMID: 28794341)
      Biochim Biophys Acta. 2012 Aug;1823(8):1389-94. (PMID: 22705155)
      Mol Med Rep. 2017 Dec;16(6):8092-8102. (PMID: 28983603)
      J Diabetes Res. 2017;2017:3797802. (PMID: 28512642)
      J Diabetes Metab. 2015 May 10;6(6):null. (PMID: 26213634)
      J Physiol Sci. 2009 Sep;59(5):377-82. (PMID: 19536612)
      Toxicol Appl Pharmacol. 2015 Feb 1;282(3):297-310. (PMID: 25541178)
      J Diabetes Res. 2016;2016:4157313. (PMID: 27725943)
      Cell Death Dis. 2018 Sep 20;9(10):950. (PMID: 30237561)
      Diabetes Care. 2005 Jun;28(6):1303-10. (PMID: 15920043)
      Biomed Pharmacother. 2017 Jun;90:562-574. (PMID: 28407577)
      Mol Cell Endocrinol. 1995 Feb 27;108(1-2):193-8. (PMID: 7758835)
      Cell Transplant. 2015;24(8):1615-26. (PMID: 24978858)
      Free Radic Biol Med. 2000 May 1;28(9):1317-27. (PMID: 10924851)
      Nat Rev Urol. 2012 Dec;9(12):678-90. (PMID: 23165403)
      Diabetes Obes Metab. 2010 Nov;12(11):994-1003. (PMID: 20880346)
      Kidney Blood Press Res. 2017;42(2):369-378. (PMID: 28624830)
      Diabetes Obes Metab. 2016 Oct;18(10):990-8. (PMID: 27282621)
      J Biol Chem. 2001 Aug 10;276(32):30188-98. (PMID: 11402028)
      Oxid Med Cell Longev. 2018 Dec 2;2018:2917387. (PMID: 30622665)
      Biochim Biophys Acta. 2012 Feb;1820(2):84-9. (PMID: 22146232)
      J Clin Invest. 1995 Feb;95(2):690-8. (PMID: 7860750)
      Am J Transl Res. 2018 Aug 15;10(8):2445-2456. (PMID: 30210683)
    • Accession Number:
      0 (Hypoglycemic Agents)
      0 (Insulin)
      0 (NF-E2-Related Factor 2)
      0 (NF-kappa B)
      0 (Nfe2l2 protein, rat)
      4Y8F71G49Q (Malondialdehyde)
      EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
      EC 1.14.14.18 (Hmox1 protein, rat)
    • Publication Date:
      Date Created: 20191005 Date Completed: 20200227 Latest Revision: 20200227
    • Publication Date:
      20221213
    • Accession Number:
      PMC6748178
    • Accession Number:
      10.1155/2019/8712492
    • Accession Number:
      31583254