title: The tACE/Angiotensin (1-7)/Mas Axis Protects Against Testicular Ischemia Reperfusion Injury.
abstract: OBJECTIVE
  To investigate whether exogenous angiotensin (Ang)-(1-7) administration can protect against the damaging consequences of testicular ischemia reperfusion (tIR) injury.
  
  
  METHODS
  Eighteen male Sprague-Dawley rats were divided equally among the following 3 groups: sham, unilateral tIR injury (1 hour of ischemic treatment and 4 hours of reperfusion), and tIR + Ang-(1-7) (0.3 mg/kg). Testicular tissues obtained from the rats were evaluated for the expression of testicular angiotensin-converting enzyme (tACE), Ang-(1-7), and the Ang-(1-7)-specific receptor Mas by immunohistochemistry and enzyme-linked immunosorbent assay. Reduced spermatogenesis, induction of the caspase-8 pathway, and nitric oxide (NO) generation were assessed. The effects of tIR and Ang-(1-7) treatment on the PI3K/Akt antiapoptosis pathway were also investigated.
  
  
  RESULTS
  Testicular morphological changes and reduced spermatogenesis associated with decreased expression of the tACE/Ang-(1-7)/Mas axis were observed during tIR. These effects were also accompanied by increased activity of caspase-3 and -8, downregulation of the survivin and BAD transcripts, and decreased NO formation. During tIR, PTEN expression was increased, leading to inactivation of the PI3K/Akt pathway. Acute treatment with Ang-(1-7) prior to reperfusion attenuated the tIR-induced damage described above.
  
  
  CONCLUSIONS
  Expression of the tACE/Ang-(1-7)/Mas axis was downregulated during tIR. Administration of exogenous Ang-(1-7) prior to reperfusion rescued tACE and Mas expression and protected against germ cell apoptosis and oxidative stress. Increased NO generation and activation of the PI3K/Akt signaling pathway may have partially contributed to these effects. The tACE/Ang-(1-7)/Mas axis likely plays a role in the maintenance of normal testis physiology and spermatogenesis.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Kuwait University, Jabriyah, Kuwait. Electronic address: malmaghrebi@hsc.edu.kw.
authors.forename: May
authors.initials: M
authors.lastname: Al-Maghrebi
authors.affiliation: Department of Anatomy, Faculty of Medicine, Kuwait University, Jabriyah, Kuwait.
authors.forename: Waleed M
authors.initials: WM
authors.lastname: Renno
mesh_terms: D000803:Angiotensin I / Q000502:physiology* / Q000627:therapeutic use*; D000818:Animals; D008297:Male; D010446:Peptide Fragments / Q000502:physiology* / Q000627:therapeutic use*; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis* / Q000502:physiology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D013737:Testis / Q000098:blood supply* / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C118790:angiotensin I (1-7)