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

J Diabetes Res. 2019 Sep 5:2019:8712492. doi: 10.1155/2019/8712492. eCollection 2019.

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-κB 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-κB pathways.

MeSH terms

  • Animals
  • Diabetes Complications / drug therapy
  • Diabetes Complications / metabolism
  • Diabetes Complications / pathology
  • Diabetes Complications / surgery*
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / surgery*
  • Heme Oxygenase (Decyclizing) / metabolism
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Insulin / pharmacology
  • Insulin / therapeutic use
  • Islets of Langerhans Transplantation*
  • Male
  • Malondialdehyde / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Sperm Count
  • Testicular Diseases / drug therapy
  • Testicular Diseases / metabolism
  • Testicular Diseases / pathology
  • Testicular Diseases / surgery*
  • Testis / drug effects
  • Testis / metabolism*
  • Testis / pathology

Substances

  • Hypoglycemic Agents
  • Insulin
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, rat
  • Malondialdehyde
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat