Phoenixin-14 ameliorates acetic acid-induced ulcerative colitis in rats via antioxidant, anti-inflammatory and anti-apoptotic mechanisms

Buzcu H., YÜKSEL M., KIRMIZIKAN S., Çikler E., Karakoyun B.

Peptides, cilt.192, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 192
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1016/j.peptides.2025.171431
  • Dergi Adı: Peptides
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Animal Behavior Abstracts, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, Veterinary Science Database
  • Anahtar Kelimeler: Acetic acid, Apoptosis, Cetrorelix, Inflammation, Oxidative stress, Phoenixin-14, Ulcerative colitis
  • İstanbul Kent Üniversitesi Adresli: Evet

Özet

Phoenixin (PNX), first discovered in the rat hypothalamus, was initially identified as a reproductive peptide. PNX-14 (14 amino acid isoform) has also been shown to function in cardiovascular regulation, neuroprotection, glucose metabolism, appetite, anxiety, and memory. We aimed to investigate the potential therapeutic role of PNX-14 in acetic acid (AA)-induced ulcerative colitis. Rats were given intrarectally 1 ml saline (control) or 5 % AA (colitis groups). The control group was treated intraperitoneally with saline, while the colitis groups were treated intraperitoneally with saline or PNX-14 (50 μg/kg/d) or gonadotrophin-releasing hormone (GnRH)-antagonist cetrorelix (CTX; 100 µg/kg/d) or CTX and PNX-14 or sulfasalazine as a positive control (100 mg/kg/d) instantly and once a day for 3 days following colitis induction. Colonic samples were evaluated histologically and biochemically [malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), chemiluminescence (CL), pro-inflammatory cytokines (tumor necrosis factor-α, interferon-γ, interleukin (IL)-1β, IL-6, IL-8), caspase-3, and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measurements] on the 3rd day. Elevated damage scores (macroscopic and microscopic), MPO, MDA, caspase-3, cytokines, and CL values, and decreased GSH levels of the colitis group were reversed by PNX-14 treatment (p < 0.05–0.001). CTX or CTX plus PNX-14 reduced damage scores, caspase-3, 8-OHdG, cytokines, and CL values (p < 0.05–0.001). Sulfasalazine treatment improved all parameters except MDA and GSH. PNX-14, which alleviates macroscopic, histological and biochemical parameters, can be considered as a potential therapeutic agent in ulcerative colitis with its anti-inflammatory, antioxidant and anti-apoptotic actions. Furthermore, despite its effects as an GnRH-antagonist, CTX has also revealed a similar beneficial role as PNX-14 in this ulcerative colitis model.