Acute kidney injury induced by glycerol is worsened by orchiectomy and attenuated by testosterone replacement

Samira Itana de Souza1, Edilene Cândido Rocha1, Halanna Rocha Ferraz1

  • 1Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista, Bahia 45029-094, Brazil.

Steroids
|November 10, 2020
PubMed

Insights

Orchiectomy worsened kidney injury in male rats, but testosterone replacement therapy mitigated this damage. This study highlights testosterone's protective role in acute kidney injury.

Area of Science:

  • Nephrology
  • Endocrinology
  • Toxicology

Background:

  • Male sex is a risk factor for renal disease, yet androgens may offer renal protection.
  • Contradictory findings exist regarding androgen effects on the kidneys.
  • No prior studies investigated orchiectomy or testosterone's impact on glycerol-induced kidney injury.

Purpose of the Study:

  • To investigate the effects of orchiectomy and subsequent testosterone replacement on acute kidney injury induced by glycerol.
  • To elucidate the role of testosterone in mitigating renal damage.

Main Methods:

  • Male Wistar rats underwent orchiectomy or sham surgery.
  • Rats were divided into four groups: sham control (NaCl), sham control (glycerol), orchiectomized (glycerol), and orchiectomized (glycerol + testosterone).
  • Testosterone was administered for 14 days; glycerol was administered to induce kidney injury. Renal function, histology, and molecular markers were assessed.

Main Results:

  • Orchiectomized rats showed increased serum creatinine, urea, and sodium excretion, indicating worsened kidney injury.
  • Testosterone administration attenuated these injury markers and reduced acute tubular necrosis.
  • Testosterone mitigated inflammatory markers (macrophages, lymphocytes, IL-1β) and apoptosis (Caspase 3), but not NF-κB.
  • Testosterone increased renal nitric oxide (NO) and attenuated increases in TNF-α, angiotensinogen, and AT1 expression.

Conclusions:

  • Orchiectomy exacerbates glycerol-induced kidney injury in male rats.
  • Testosterone replacement therapy demonstrates significant renal protective effects against acute kidney injury.
  • Testosterone may counteract kidney damage by modulating inflammatory pathways, apoptosis, and the renin-angiotensin system.

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