Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary-gonadal axis

Can J Physiol Pharmacol. 2016 Jun;94(6):651-61. doi: 10.1139/cjpp-2015-0503. Epub 2016 Jan 19.

Abstract

Chronic hyperglycemia is associated with impairment of testicular function. The current study aimed to investigate the protective effects and the possible mechanisms of taurine and pioglitazone against diabetes-induced testicular dysfunction in rats. Diabetes was induced by streptozotocin injection. Both normal and diabetic rats received taurine (100 mg/kg) or pioglitazone (10 mg/kg) orally and daily for 6 weeks. Diabetic rats showed a significant (P < 0.001) increase in glycosylated hemoglobin, glucose, homeostasis model of insulin resistance, and pro-inflammatory cytokines. Serum insulin, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly (P < 0.001) decreased in diabetic rats. Taurine and pioglitazone alleviated hyperglycemia, decreased pro-inflammatory cytokines, and increased circulating levels of insulin, testosterone, LH, and FSH. Gene and protein expression of LH and FSH receptors and cytochrome P450 17α-hydroxylase (CYP17) was significantly (P < 0.001) down-regulated in testes of diabetic rats, an effect which was significantly increased after administration of taurine and pioglitazone. In addition, taurine and pioglitazone significantly decreased lipid peroxidation and DNA damage, and enhanced activity of the antioxidant enzymes in testes of diabetic rats. In conclusion, taurine and pioglitazone exerted protective effects against diabetes-induced testicular damage through attenuation of hyperglycemia, inflammation, oxidative stress and DNA damage, and up-regulation of the pituitary/gonadal axis.

Keywords: CYP17A1; DNA fragmentation; axe hypophyso–gonadique; diabetes; diabète; dysfonction testiculaire; fragmentation de l’AND; pituitary–gonadal axis; taurine; testicular dysfunction; thiazolidinedione.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / blood
  • Male
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Pioglitazone
  • Pituitary Gland / drug effects
  • Pituitary Gland / metabolism*
  • Rats
  • Rats, Wistar
  • Taurine / pharmacology
  • Taurine / therapeutic use*
  • Testis / drug effects
  • Testis / metabolism*
  • Testis / pathology
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • Inflammation Mediators
  • Thiazolidinediones
  • Taurine
  • Pioglitazone