Effects of Combined Propranolol or Carvedilol with Mesalazine on Experimentally Induced Ulcerative Colitis in Male Albino Rats

Abstract

Background:Ulcerative colitis is a chronic disease with a complex etiology. Many studies suggest the coordination of immune and environmental factors in both the initiation and progression of the disease.Oral mesalazine (also known as mesalamine) is a 5-aminosalicylic acid compound used in the treatment of mild to moderate Ulcerative Colitis (UC).Beta blockers are available and widely used drugs with established antioxidant actions, our aim wasto figure out the beneficial effects of propranolol, carvedilol and mesalazineand Their Interaction with Mesalazine on Ulcerative Colitis development, to distinguish which of them offer greater beneficial effect on experimentally induced ulcerative colitis in male albino rats.
Materials and Methods: The study was done on 50males Wistar albino rats that randomly allocated to five groups, with each group comprising eleven rats except control group composed of six rats. Group I: control group, Group: ulcerative colitis group, Group III:mesalazine pretreated (300 mg/kg/d), Group IV: propranolol (30 mg/kg) + mesalazine (300 mg/kg) group, Group V:carvedilol (30 mg/kg) +mesalazine (300 mg/kg) group. To induce Ulcerative colitis, they were starved from all foods and allowed to drink water for 12 hours. Every rat was housed in separate cage with high mesh to prevent coprophagy (ingestion of hair and feces). They were divided into 5 groups 1st control group (6 rats), 2nd Ulcerative colitis group (11 rats), 3rdmesalazine pretreated group (11 rats). 4thPropranolol plus Mesalazine -pretreated group: (n = 11 rats), 5thCarvedilol plus Mesalazine -pretreated group: (n = 11 rats). Results:
In UC group, colon W/L ratio, CW/BW ratio were decreased, and it decreased significantly also in Propranolol plus mesalazine group and Carvedilol plus mesalazine group. The mean microscopic scores of mucosal damage were significantly decreased in both Propranolol plus mesalazine and Carvedilol plus mesalazine groups.In carvedilol plus mesalazine group, colonic SOD levelwas significantly higher than that of ulcerative colitis, carvedilol and mesalazine pretreated groups.Carvedilol plus mesalazine group, colonic IL-1βlevel significantly decreased in UC group to lower than that of carvedilol and mesalazine pretreated groups.Propranolol plus mesalazine group, colonic pERK1/2/ non-pERK1/2 ratio significantly) increased. In Carvedilol plus
Mesalazine pretreated group colonic pERK1/2/ non-pERK1/2 ratio significantlyincreased higher than that of carvedilol and mesalazine pretreated groups. Conclusion:Propranolol and carvedilol had a beneficial effect against experimentally induced colitis depending on their ability to decreases inflammation, oxidative stress state in rat colon. Carvedilol combination synergized the ameliorative effects of mesalazine compared to mesalazine alone. Thus, carvedilol can be considered the β-blocker of benefit in UC treatment especially during treatment of other coexisting diseases indicated β-blockers. Additional clinical trials are advised to clarify their effectiveness in UC.