Evaluation of the effect of antibiotics, anti-inflammatory agent, and monoclonal antibody on the gastrointestinal tract in a rat model of acetic acid-induced ulcerative colitis

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by gut pathology and impaired gut function. This study aimed to evaluate the efficacy of antibiotic, anti-inflammatory, and monoclonal antibody therapies on gut pathology in a rat model of acetic acid-induced UC.

Fifty Adult Male Sprague-Dawley rats were divided into five groups of ten rats each, the animals were allowed to acclimatize for a period of 2 weeks. The induction of the ulcerative colitis was done according to the method described by Al-Rejaie et al., (2013), after 24 hours fast, 2 ml of 4% acetic acid solution was administered transrectally using a (2.7 mm) soft pediatric catheter. After acetic acid administration, rats were holed horizontally for 2 min to prevent acetic acid leakage. Manifestation of Ulcerative Colitis was observed in the rats after 6 days of induction and treatment was carried out for a period of 42 days.  Group A was the normal control. UC was induced with 2 ml of 4% acetic acid solution transrectally using soft pediatric catheter in Group B while, Group C and D received 40 mg/kg of Ciproflaxin and 100 mg/kg of Prednisolone respectively every 72 hours for forty-two days orally, and Group E received 5 mg/kg of infliximab for 2 weeks Intraperitoneally. At the end of 42 days, Total acidity, Gastric mucus concentration and pH were determined using standard method; MDA- Lipid Peroxidation was also determined in the stomach, pancreas, small and large intestine. The Histoarchitecture of the stomach, small and large intestine were studied.

The UC-induced group showed significant changes in gut physiology and pathology, including decreased pH, increased total acidity, reduced mucin content, elevated malondialdehyde (MDA) levels, and increased clinical symptoms. In contrast, all treatment groups showed significant improvements in gut physiology, contributing positively to ameliorating the symptoms and pathological features of ulcerative colitis with varying efficacy. Histological analysis revealed significant pathological changes in the UC-induced group, including thickened muscularis, degenerated mucosa, and compromised submucosa, which were improved in the anti-inflammatory-treated and monoclonal antibody-treated groups.

The study effectively highlights the significant impacts of antibiotic, anti-inflammatory agent and monoclonal antibody in improving in gut physiology on various parameters associated with UC potentially through the regulation of gastrointestinal secretions, reduction of pro-inflammatory cytokines, which contribute to UC severity, inhibition of oxidative stress, which can damage the gut barrier and exacerbate UC, increase in mucin content, which can protect the gut barrier and reduce UC severity, and modulation of the gut microbiome, which can influence UC severity. The findings indicate that while all the three interventions contribute positively to ameliorating the symptoms and pathological features of UC, their overall efficacy vary. This study provides insights into the efficacy of the different therapies on gut pathology in UC and may inform the development of novel treatments for this debilitating disease.