Combination Therapy of Allopurinol and Dantrolene and Its Role In The Prevention of Experimental Ischemia Reperfusion Injury Of The Small Intestine

Abstract

Background The effect of different drugs on ischemia and reperfusion (I/R; induced oxygen free radical damage) was examined in small bowel tissue because the intestine is extremely sensitive to this pathology. Different drugs (allopurinol and dantrolene) can remove oxygen free radicals or inhibit the mechanisms leading to their generation, thus reducing mucosal lesions. We investigated the protective potential of combination therapy in the intestine against I/R damage. Methods Forty-eight male Wistar rats were separated into 8 groups: one sham (control), one I/R (ischemia 60 min + reperfusion at 24 h), and 6 groups treated with allopurinol, dantrolene, or combination therapy. The grade of injury in the small bowel was established by the lipid peroxidation (MDA) and antioxidant enzymatic activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in tissue samples. Moreover, the collected samples were subjected to histological study. Results Combination therapy preserved normal enzymatic levels compared to the I/R groups (p < 0.05) for all parameters studied. The animals treated with combination therapy showed less severe small bowel damage than I/R group in accordance with the histological results. Conclusions Results obtained in the experimental process indicate that the administration of antioxidants protects against intestinal damage by I/R. Overall, combination therapy may protect intestinal tissue from I/R injury.

Keywords

• intestinal ischemia/reperfusion
• allopurinol
• dantrolene
• antioxidant enzyme activity
• oxygen free radicals