Effect of Pomegranate Juice on Intestinal Recovery Following Methotrexate-Induced Intestinal Damage in a Rat Model

ABSTRACT

Background/Aims: Several studies have demonstrated the antimicrobial, antihelminthic, and antioxidant potential of the active ingredients of pomegranate (PMG) extracts, suggesting their preventive and curative role in several gastrointestinal disorders. In the present study, the authors evaluated the effects of oral PMG supplementation on intestinal structural changes, enterocyte proliferation, and apoptosis during methotrexate (MTX)-induced intestinal damage in a rat.

Methods: Male rats were divided into 4 experimental groups: control rats; CONTR-PMG rats were treated with oral PMG given by gavage once a day 72 hours before and 72 hours following vehicle injection; MTX rats were treated with single dose of methotrexate; and MTX-PMG rats were treated with oral PMG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 72 hours following MTX injection. Western blotting was used to determine phosphorylated extracellular signal–regulated kinase (p-ERK) and caspase 3 protein levels.

Results: MTX-PMG rats demonstrated greater jejunal and ileal bowel and mucosal weights, greater jejunal and ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared with MTX animals. A significant decrease in enterocyte apoptosis in ileum of MTX-PMG rats (vs MTX) was associated with a decrease in caspase 3 protein expression as well as increased cell proliferation, which was correlated with elevated p-ERK protein levels.

Conclusions: Treatment with oral PMG prevents mucosal injury and improves intestinal recovery following MTX injury in the rat.

KEYWORDS:

• Intestine
• methotrexate
• mucositis
• PMG
• rat

Acknowledgments

The authors thank Bio-Rad Laboratories Inc. (Technion Campus, 32000 Haifa, Israel) for assistance with Western blot analysis.