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

Authors’ contributions

Beatriz Prieto-Moure: Performing laboratory controls (analysis and interpretation data), handling animals and surgical technics. Review of literature and article texts. Dolores Cejalvo-Lapeña: General coordinator of the research project. Monitoring animal management. Quality control of the process. Review of literature and article texts. Mariola Belda-Antolí: Performing laboratory controls (analysis and interpretation data), handling animals and surgical technics. Review of literature and article texts. Carolina Padrón-Sanz: General coordinator of the research project; design of experiments; Review of literature and article texts. Jose Miguel Lloris-Cejalvo: Animal laboratory management (housing; anesthesia, surgical technics) and bibliographic review. Jose Miguel Lloris-Carsí: Project Director; training in experimental surgery team; review of literature and article texts; statistical treatment of data.

Disclosure statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Additional information

Funding

The authors acknowledge the funds provided by the Catholic University of Valencia, Spain.