Cilostazol alleviates streptozotocin-induced testicular injury in rats via PI3K/Akt pathway

Life Sci. 2018 Apr 1:198:136-142. doi: 10.1016/j.lfs.2018.02.038. Epub 2018 Feb 27.

Abstract

Aims: Male infertility prevalence is higher in diabetic patients. Those patients exhibit testicular oxidative damage due to sustained hyperglycemia and inflammation. The study has investigated the efficacy of cilostazol, a phosphodiesterase 3 inhibitor, on testicular damage of diabetic rats.

Main methods: Streptozotocin-induced diabetes in rats was used as a model. Six control male rats and 24 diabetic male rats were divided into the following: diabetic, cilostazol at low dose, cilostazol at high dose, and sildenafil treated rat groups. Treatment period was 4 weeks. Then, serum testosterone, testicular oxidative parameters, and testicular oxidant defenses were assayed. Real time PCR was done for quantification of Phosphoinositide 3-kinase (PI3K), Akt, and nuclear factor (NF)-κB mRNA. Expression of testicular inducible nitric oxide synthase (iNOS) was assessed.

Key findings: Diabetes negatively affected the testicular tissue as evident by biochemical analysis and histopathology. Four weeks of cilostazol or sildenafil treatment improved anti-oxidative capacity, ameliorated lipid peroxidation and the pro-inflammatory iNOS expression in testicular tissue. Testosterone level and the spermatogenesis showed marked improvement. Quantitative mRNA expression showed an elevation in PI3K and Akt by cilostazol with decreasing in NF-κB level by both drugs.

Significance: Our findings suggest the beneficial role of cilostazol and sildenafil in diabetic testicular damage dependent on anti-inflammatory and anti-oxidant effects.

Keywords: Cilostazol; Diabetic testicular damage; Sildenafil.

MeSH terms

  • Animals
  • Cilostazol
  • Diabetes Complications / metabolism*
  • Diabetes Mellitus, Experimental / metabolism
  • Glutathione / metabolism
  • Heme Oxygenase (Decyclizing) / metabolism
  • Hyperglycemia / metabolism
  • Infertility, Male / drug therapy*
  • Inflammation
  • Male
  • Malondialdehyde / metabolism
  • Oxygen / chemistry
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphodiesterase 3 Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Sildenafil Citrate / pharmacology
  • Streptozocin
  • Superoxide Dismutase / metabolism
  • Testis / drug effects*
  • Testis / injuries
  • Tetrazoles / pharmacology*

Substances

  • Phosphodiesterase 3 Inhibitors
  • Tetrazoles
  • Malondialdehyde
  • Streptozocin
  • Sildenafil Citrate
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • Superoxide Dismutase
  • Phosphatidylinositol 3-Kinases
  • Akt1 protein, rat
  • Proto-Oncogene Proteins c-akt
  • Glutathione
  • Cilostazol
  • Oxygen