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

Abstract

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 param eters, can be considered as a potential therapeutic agent in ulcerative colitis with its anti-inflammatory, anti oxidant 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.