N-acetylserotonin protects against renal ischemia-reperfusion injury by exhibiting antioxidant, anti-inflammatory and antiapoptotic effects through regulation of Nrf2 and TLR4/NF-κB/iNOS expression

KIRGIZ Ö., Kazak Akcakavak F., Ceren Kirgiz F., ALAKUŞ İ., KARATAŞ Ö., ALAKUŞ H., ...Daha Fazla

Tissue and Cell, cilt.102, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 102
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1016/j.tice.2026.103549
  • Dergi Adı: Tissue and Cell
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE
  • Anahtar Kelimeler: INOS expression, N-acetylserotonin, Nrf2 pathway, Oxidative stress, Renal ischemia-reperfusion, TLR4/NF-κB signaling
  • Sivas Cumhuriyet Üniversitesi Adresli: Evet

Özet

Background: Renal ischemia-reperfusion (RIR) injury is one of the main causes of acute kidney injury, and different processes such as oxidative stress, inflammation and apoptosis play important roles in its pathogenesis. N-acetylserotonin (NAS) is known as an intermediate metabolite in the melatonin synthesis pathway between serotonin and melatonin, and the potential effects of NAS on RIR injury are not yet clear. Methods: Twenty-eight male Wistar albino rats were randomly divided into 4 groups (n = 7). The sham group underwent laparotomy only. The NS group received 20 mg/kg NAS intraperitoneal (i.p.) 45 min before laparotomy. The I/R group underwent renal artery clamping for 45 min to induce ischemia/reperfusion injury without any pharmacological agents, followed by 24 h of reperfusion. The NI/R group received 20 mg/kg i.p. NAS 45 min prior to ischemia/reperfusion injury, and the renal artery was clamped for 45 min, followed by 24 h of reperfusion. Oxidative stress parameters, histopathological and immunohistochemical changes were examined. Results: NAS pretreatment significantly decreased malondialdehyde (MDA) levels (P < 0.01) and restored antioxidant parameters including glutathione (GSH) levels, catalase (CAT) and glutathione peroxidase-1 (GPx1) enzyme activities compared to the I/R group (P < 0.01). Histopathological injury scores (tubular degeneration, necrosis, inflammatory infiltration, and hyaline casts) were markedly lower in the NI/R group compared to the I/R group (P<0.01). Furthermore, immunohistochemical analysis showed that NAS pretreatment suppressed the expression of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and caspase-3, and increased the expression of nuclear factor erythroid 2-associated factor 2 (Nrf2) (P<0.01). Conclusion: All results indicate that NAS is an effective agent in protecting kidney tissue against RIR injury by exhibiting antioxidant, anti-apoptotic and anti-inflammatory properties.