Maria Grazia Zizzo1,2, Gaetano Caldara3, Annalisa Bellanca4, Domenico Nuzzo5, Marta Di Carlo5, Rosa Serio3. 1. Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Laboratorio di Fisiologia generale, Università di Palermo, Viale delle Scienze, 90128, Palermo, Italy. mariagrazia.zizzo@unipa.it. 2. ATeN (Advanced Technologies Network) Center, Università di Palermo, Viale delle Scienze, 90128, Palermo, Italy. mariagrazia.zizzo@unipa.it. 3. Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Laboratorio di Fisiologia generale, Università di Palermo, Viale delle Scienze, 90128, Palermo, Italy. 4. ATeN (Advanced Technologies Network) Center, Università di Palermo, Viale delle Scienze, 90128, Palermo, Italy. 5. Istituto di Biomedicina ed Immunologia Molecolare (IBIM) "Alberto Monroy", CNR, 90146, Palermo, Italy.
Abstract
BACKGROUND: Guanosine, a guanine-based purine, is an extracellular signaling molecule exerting anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. We aimed to investigate its protective effects on 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rat. METHODS: Rats were divided into five groups and colitis was induced by intracolonic instillation of DNBS (15 mg/rat). Guanosine (4 or 8 mg/kg) was administered for 6 days i.p. starting the day of the colitis induction. Body weight loss, stool consistency, colon weight/length, histological analysis, myeloperoxidase activity (MPO) and pro-inflammatory cytokine levels were assessed. Immunoblotting of nuclear factor-κB (NF-κB) p65 protein levels and detection of oxidative and nitrosative stress markers were also performed. RESULTS: Guanosine, in a dose-dependent manner, significantly ameliorated the severity of DNBS-induced colitis, reducing body weight loss and diarrhea incidence, preventing the DNBS-induced macroscopic and microscopic damage to the colonic mucosa, and the MPO increase. Guanosine treatment also lowered interleukin-1β, interleukin-6, and tumor necrosis factor-α mRNA levels. Importantly, guanosine in DNBS rats down-regulated the expression of NF-κB p65 and the levels of reactive oxygen species and nitrite. CONCLUSIONS: In conclusion, guanosine exerts beneficial effects in DNBS-induced colitis in rats, through modulation of colonic inflammation, downregulating of NFκB-mediated signaling.
BACKGROUND:Guanosine, a guanine-based purine, is an extracellular signaling molecule exerting anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. We aimed to investigate its protective effects on 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rat. METHODS:Rats were divided into five groups and colitis was induced by intracolonic instillation of DNBS (15 mg/rat). Guanosine (4 or 8 mg/kg) was administered for 6 days i.p. starting the day of the colitis induction. Body weight loss, stool consistency, colon weight/length, histological analysis, myeloperoxidase activity (MPO) and pro-inflammatory cytokine levels were assessed. Immunoblotting of nuclear factor-κB (NF-κB) p65 protein levels and detection of oxidative and nitrosative stress markers were also performed. RESULTS:Guanosine, in a dose-dependent manner, significantly ameliorated the severity of DNBS-induced colitis, reducing body weight loss and diarrhea incidence, preventing the DNBS-induced macroscopic and microscopic damage to the colonic mucosa, and the MPO increase. Guanosine treatment also lowered interleukin-1β, interleukin-6, and tumor necrosis factor-α mRNA levels. Importantly, guanosine in DNBSrats down-regulated the expression of NF-κB p65 and the levels of reactive oxygen species and nitrite. CONCLUSIONS: In conclusion, guanosine exerts beneficial effects in DNBS-induced colitis in rats, through modulation of colonic inflammation, downregulating of NFκB-mediated signaling.
Authors: Edwin K Jackson; Georgios D Kitsios; Michael Y Lu; Caitlin M Schaefer; Cathy J Kessinger; Bryan J McVerry; Alison Morris; Bernard J C Macatangay Journal: Sci Rep Date: 2022-10-17 Impact factor: 4.996