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Background <p>Renal ischemia–reperfusion injury (IRI) triggers oxidative stress and apoptosis, culminating in acute kidney injury. Agomelatine (AGO), a melatonergic agent with antioxidant/anti-inflammatory activity, may afford renoprotection.</p> Methods <p>Thirty-two female Wistar albino rats were randomized to: sham (right nephrectomy); IR (right nephrectomy + 60-min left renal pedicle clamping; 24-h reperfusion); IR + AGO (25&#xa0;mg/kg <i>per os</i> immediately before reperfusion); and AGO + IR (25&#xa0;mg/kg per os 30&#xa0;min before ischemia). Outcomes included serum blood urea nitrogen (BUN)/creatinine (Cr); renal malondialdehyde (MDA), total oxidative status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), protein carbonyl (PC); periodic acid schiff (PAS) histology (tubular casts, brush-border loss, glomerular changes, intratubular macrophages); and caspase-3 immunohistochemistry.</p> Results <p>IRI elevated BUN/Cr and oxidative indices (MDA, TOS, OSI, PC) and decreased TAC versus sham (<i>p</i> &lt; 0.001). AGO significantly lowered BUN/Cr, MDA, TOS, OSI, and PCs while increasing TAC versus IRI (<i>p</i> &lt; 0.001). Glomerular changes were significantly increased in the IR group compared with sham, while both AGO-treated groups showed lower scores. However, no significant difference was observed between the two AGO treatment regimens.</p> Conclusion <p>AGO confers acute renoprotection against IRI by restoring antioxidant capacity and attenuating oxidative protein/lipid damage and apoptosis. Pre-ischemic dosing outperformed post-ischemic dosing<b>,</b> underscoring the importance of timing. These data support AGO as a prophylactic candidate for procedures with predictable renal ischemia.</p>

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Agomelatine reduces oxidative stress and apoptosis in renal ischemia reperfusion injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月20日

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  • Onural Ozhan,
  • Orhan Turfan,
  • Ahmet Acet,
  • Azibe Yildiz,
  • Alaadin Polat,
  • Nigar Vardi,
  • Mehmet Demir,
  • Hakan Parlakpinar

摘要

Background

Renal ischemia–reperfusion injury (IRI) triggers oxidative stress and apoptosis, culminating in acute kidney injury. Agomelatine (AGO), a melatonergic agent with antioxidant/anti-inflammatory activity, may afford renoprotection.

Methods

Thirty-two female Wistar albino rats were randomized to: sham (right nephrectomy); IR (right nephrectomy + 60-min left renal pedicle clamping; 24-h reperfusion); IR + AGO (25 mg/kg per os immediately before reperfusion); and AGO + IR (25 mg/kg per os 30 min before ischemia). Outcomes included serum blood urea nitrogen (BUN)/creatinine (Cr); renal malondialdehyde (MDA), total oxidative status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), protein carbonyl (PC); periodic acid schiff (PAS) histology (tubular casts, brush-border loss, glomerular changes, intratubular macrophages); and caspase-3 immunohistochemistry.

Results

IRI elevated BUN/Cr and oxidative indices (MDA, TOS, OSI, PC) and decreased TAC versus sham (p < 0.001). AGO significantly lowered BUN/Cr, MDA, TOS, OSI, and PCs while increasing TAC versus IRI (p < 0.001). Glomerular changes were significantly increased in the IR group compared with sham, while both AGO-treated groups showed lower scores. However, no significant difference was observed between the two AGO treatment regimens.

Conclusion

AGO confers acute renoprotection against IRI by restoring antioxidant capacity and attenuating oxidative protein/lipid damage and apoptosis. Pre-ischemic dosing outperformed post-ischemic dosing, underscoring the importance of timing. These data support AGO as a prophylactic candidate for procedures with predictable renal ischemia.