From a Molecular Biological Viewpoint, Does Endothelin Type A Receptor Antagonist Therapy Reduce Diabetes-induced Testicular Damage in Rats?

Objectives

To evaluate the therapeutic effects of a selective endothelin type A receptor antagonist (ERA-A) on testis of streptozotocin (STZ)–induced diabetic rats.

Methods

Eighty rats were analyzed in 4 groups: healthy controls, diabetic rats, diabetic rats treated with ERA-A, and healthy rats treated with ERA-A. Diabetes was induced in 40 rats by a single intraperitoneal injection of STZ and followed for 2 months. A total of 20 diabetic and 20 healthy rats were also intravenously treated with ERA-A at days 7 and 15. The remaining untreated healthy rats served as controls. Blood glucose levels of ≥ 250 mg/dL were considered to indicate diabetes and were measured at the end of the second month. Formalin-fixed paraffin-embedded testis tissue sections were analyzed after staining with hematoxylin and eosin or specific antibodies for apoptotic markers. mRNA expressions of genes involved in the apoptotic pathway or spermatogenesis were evaluated by real-time reverse transcription–polymerase chain reaction.

Results

Major therapeutic effects of ERA-A could be achieved for damages caused by oxidative stress. Although a decrease in apoptotic cell death could be detected, no statistically meaningful results could be obtained for the duration of spermatogenesis.

Conclusions

ERA-A could prevent germ cell death by apoptosis and testicular damage in diabetic rats.