Sildenafil attenuates nonsteroidal anti‐inflammatory‐induced gastric ulceration in mice via antioxidant and antigenotoxic mechanisms. (18th October 2020)

• Record Type: Journal Article
• Authors: Maziero Alves, Gisele; Aires, Rafaela; de Souza Santos, Verônica; Zambom Côco, Larissa; Peters, Beatriz; de Leone Evangelista Monteiro Assis, Arícia; Ramos Athaydes, Brena; Gobbi Amorim, Fernanda; Valentim Nogueira, Breno; de Ribeiro Gonçalves, Rita Cássia; dos Santos Meyrelles, Silvana; Melo Costa Pereira, Thiago; Prandi Campagnaro, Bianca
• Is Part Of: Clinical and experimental pharmacology and physiology. Volume 48:Number 3(2021)
• Page Start: 401
• Page End: 411
• Publication Date: 2020-10-18
• Subjects: cGMP -- gastric mucosa -- gastric ROS production -- NO -- NSAIDS -- PDE5 inhibitor; Clinical pharmacology -- Periodicals; Pharmacology, Experimental -- Periodicals; Physiology, Experimental -- Periodicals; Physiology, Pathological -- Periodicals; 615.1
• DOI: 10.1111/1440-1681.13414
• Languages: English
• ISSNs: 0305-1870

Abstract

Abstract: Sildenafil (SIL) has potential as an interesting gastroprotective drug. However, the pathways of its protective effect still needs to be clarified, and its use as a potential gastroprotective agent validated. This study aims to evaluate the effects of SIL via modulation of oxidative stress in a NSAID‐induced gastric lesion model. Male Swiss mice were divided into six groups: control (CON, water), nonsteroidal anti‐inflammatory drug (NSAID, water), proton pump inhibitor (PPI, 30 mg/kg of lansoprazole), SIL 5 (5 mg/kg), SIL 25 (25 mg/kg) and SIL 50 (50 mg/kg). The animals were treated by gavage (a single dose) after 24 hours of fasting, and gastric lesions were performed after 30 minutes, with indomethacin (40 mg/kg, by gavage). After 6h, the animals were killed and the stomach was removed to evaluate reactive oxygen species (ROS) production, oxidation of macromolecules, quantification of antioxidant enzymes, DNA fragmentation, apoptosis and macroscopic and histologic analysis of gastric lesions. SIL exerts a dose‐dependent gastroprotective effect against NSAID‐induced mucosal injury, also reducing cytoplasmic levels of ROS and consequent oxidative damage to macromolecules. In addition, SIL increases nitric oxide bioavailability, antioxidant enzymes and gastric cellular viability, as well as restoring important factors involved in gastroprotection. Our results demonstrate that different doses of SIL prevent indomethacin‐induced gastric ulcer in mice via different, but complementary antioxidant, antigenotoxic and antiapoptotic mechanisms. Abstract : Sildenafil prevent indomethacin‐induced gastric ulcer in mice via different but complementary antioxidant, antigenotoxic and antiapoptotic mechanisms. Sildenafil might be applicable in preventing the gastric effects of NSAIDS in a clinical investigation as alternative/complemental to peptic ulcer management.