THE EFFECTS OF ALLOPURINOL ON REDOX SENSITIVE TRANSCRIPTION FACTORS, PRO- INFLAMMATORY CYTOKINES AND HEME OXYGENASE-1 IN ACETIC ACID-INDUCED COLITIS IN RATS

ULVI DEMIREL¹, MEHMET YALNIZ¹, CEMAL ORHAN², NURETTIN TUNC¹, ABDURRAHMAN SAHIN¹, MEHMET TUZCU³, KAZIM SAHIN², IBRAHIM HANIFI OZERCAN⁴, IBRAHIM HALIL BAHÇECIOGLU¹

¹Department of Gastroenterology, School of Medicine, Firat University, Elazig, Turkey - ²Department of Animal Nutrition, Faculty of Veterinary Science, Firat University, Elazig, Turkey - ³Department of Biology, Faculty of Science, Fırat University, Elazig, Turkey - ⁴Department of Pathology, School of Medicine, Firat University, Elazig, Turkey

Introduction: Oxidative stress plays an important role in pathophysiology of inflammatory bowel diseases. We aimed to inve- stigate the effects of antioxidant allopurinol (AP) and the potential mechanisms leading amelioration upon acetic acid induced coli- tis.

Materials and methods: Twenty-eight rats were divided in four groups. Control rats received 1 mL of NaCl (0.9%). In the AA group rats received 1 mL of 5% (v/v) acetic acid. The rats in the AAAP group received 1 mL of 5% (v/v) acetic acid. Additionally these rats received 100 mg/kg AP. AP group rats received only 100 mg/kg AP. Histopathological, biochemical and western blot analy- sis were done.

Results: In the AA group, colonic injury scores, malondialdehyde (MDA), NF-κB p65, TNFα, COX2, AP-1 and IL-6 levels were significantly higher than in the control group (P<0.05). In the AAAP treatment group the colonic injury scores, MDA, NF-κB p65, TNFα, COX2, AP-1 and IL-6 levels significantly decreased when compared to the AA treated rats (P<0.05). The expression of HO-1 in the AAAP group significantly increased when compared to the AA treated rats (P<0.05).

Conclusion: Intra colonic acetic acid instillation causes severe intestinal injury accompanied to increased oxidative stress. AP treatment ameliorates this injury by overcoming oxidative stress and regulating cellular redox balance in favor of antioxidant defense mechanisms probably via manipulation of redox sensitive transcription factors.