SINAPIC ACID ATTENUATES MITOCHONDRIAL STRESS AND INFLAMMATION IN DICLOFENAC-INDUCED INTESTINAL INJURY IN RATS

Introduction: Non-steroidal anti-inflammatory drug (NSAID)-associated enteropathy has become a clinical problem owing to the widespread use of these analgesics. Aim of the work: In this work, we aimed to explore the protective effects of sinapic acid against NSAIDs-induced enterocyte injury and address the possible mechanisms. Materials and Methods: 24 male rats were randomly assigned to one of four groups: Group I (CONT), Group II (Sinapic), Group III (Diclofenac), or Group IV (Diclofenac+Sinapic) groups. Rats were administered either oral saline or sinapic acid (40 mg/kg) for 5 days before the induction of intestinal injury by a single intraperitoneal injection of diclofenac (50 mg/kg), followed by scarification after 6 hours. Food intake and body weight were recorded. Serum total proteins, serum proinflammatory cytokine IL-1β, and intestinal oxidative stress markers (NO, MDA, and GSH) were measured. Specimens of small intestine were assessed by means of macroscopic and microscopic analysis using H & E and PAS stains, in addition to histoimmunological assessment for intestinal iNOS and COX-2. Results: Serum total proteins were significantly reduced, and intestinal oxidative stress markers and serum IL-1β were significantly increased in group III compared with those in the control and sinapic groups (p< 0.05). In addition, histopathological examination revealed marked mucosal erosion, decreased functioning goblet cells, and increase mean area % of intestinal iNOS and COX-2 immunoreaction. Prophylactic administration of sinapic acid significantly mitigated these abnormalities compared to the diclofenac group (p<0.05). Conclusion: The anti-inflammatory and antioxidant properties of sinapic acid make it a promising nutraceutical and pharmaceutical agent that can be useful for preventing serious intestinal enteropathy associated with NSAIDs treatment.