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ABSTRACT Purpose: Reflux esophagitis is a condition characterized by inflammation and irritation of the esophagus, resulting from the backflow of stomach acid and other gastric contents into the esophagus. Columbianadin is a coumarin derivative that exhibits anti-inflammatory and antioxidant effects. In this study, we tried to scrutinize the protective effect of Columbianadin against acute reflux esophagitis in rats. Methods: RAW 264.7 cells were utilized to assess cell viability and measure the production of inflammatory parameters. The rats received anesthesia, and reflux esophagitis was induced via ligation of pylorus and fore stomach and corpus junction. Rats received the oral administration of Columbianadin (25, 50 and 100 mg/kg) and omeprazole (20 mg/kg). The gastric secretion volume, acidity, and pH were measured. Additionally, the levels of oxidative stress parameters, cytokines, and inflammatory markers were determined. At the end of the study, mRNA expression was assessed. Results: Columbianadin remarkably suppressed the cell viability and production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and prostaglandin (PGE2). Columbianadin treatment remarkably suppressed the secretion of gastric volume, total acidity and enhanced the pH level in the stomach. Columbianadin remarkably altered the level of hydrogen peroxidase, free iron, calcium, and plasma scavenging activity, sulfhydryl group; oxidative stress parameters like malonaldehyde, glutathione, superoxide dismutase, catalase, glutathione peroxidase; inflammatory cytokines viz., TNF-α, IL-6, IL-1β, IL-10, IL-17, and monocyte chemoattractant protein-1; inflammatory parameters including PGE2, iNOS, COX-2, and nuclear kappa B factor (NF-κB). Columbianadin remarkably (P < 0.001) suppressed the mRNA expression TNF-α, IL-6, IL-1β and plasminogen activator inhibitor-1. Conclusions: Columbianadin demonstrated a protective effect against acute reflux esophagitis via NF-κB pathway. Purpose esophagus antiinflammatory anti effects study Methods 2647 264 7 264. anesthesia junction 25, 25 (25 5 10 mg/kg mgkg mg kg 20 (2 mg/kg. . volume measured Additionally determined assessed Results factorα α TNFα, TNFα TNF , (TNF-α) IL1β, IL1β ILβ IL 1β, 1β β (IL)-1β IL6, IL6 6, 6 IL-6 cyclooxygenase2 cyclooxygenase 2 cyclooxygenase- COX2, COX2 COX (COX-2) iNOS (iNOS) PGE2. PGE2 PGE (PGE2) peroxidase iron calcium activity group malonaldehyde dismutase catalase viz viz. α, TNF-α IL10, IL10 10, IL-10 IL17, IL17 17, 17 IL-17 protein1 protein 1 protein-1 2, COX-2 NFκB. NFκB NF κB (NF-κB) P 0.001 0001 0 001 inhibitor1. inhibitor1 inhibitor 1. inhibitor-1 Conclusions pathway 26 ( (TNF-α IL- (COX-2 (iNOS (PGE2 IL1 IL-1 protein- COX- (NF-κB 0.00 000 00 inhibitor- (COX- (PGE 0.0 (COX 0.