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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.
Abstract:
Although several studies have demonstrated that the male gender represents an independent risk factor for renal disease, evidence shows that androgens exert renal protective actions. The findings are controversial and no studies have evaluated the effects of orchiectomy and testosterone replacement on glycerol-induced renal injury. Male Wistar rats were submitted to orchiectomy or sham surgery and divided into four groups: SC, sham control rats injected with NaCl; SG, sham rats injected with glycerol; OG, orchiectomized rats injected with glycerol; OGT, orchiectomized rats injected with glycerol and testosterone. Testosterone was administered daily for 14 days in the OGT group. After 11 days of testosterone replacement in the OGT group, SC rats were submitted to a saline injection, while SG, OG and OGT rats received glycerol. All rats were euthanized three days after injections. OG rats presented higher serum creatinine and urea, and sodium excretion, compared to SC and SG, while testosterone attenuated these changes. Acute tubular necrosis was also mitigated by testosterone. Renal immunostaining for macrophages, lymphocytes and NF-κB was higher in OG compared to SC and SG. In addition, renal interleukin-1β, Caspase 3 and AT1 gene expression was higher in OG rats compared to SG. Testosterone attenuated these alterations, except the NF-κB immunostaining. The renal NO was lower in OG rats compared to SG. Only the OG rats presented decreases in serum NO and renal HO-1, and increased TNF-α, angiotensinogen and AT1 expression compared to SC. We conclude that orchiectomy worsened glycerol-induced kidney injury, while testosterone attenuated this renal damage.
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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