Recombinant Human Epidermal Growth Factor Alleviates Gastric Antral Ulcer Induced by Naproxen: A Non-steroidal Anti Inflammatory Drug

Gastroenterology Res. 2010 Jun;3(3):125-133. doi: 10.4021/gr2010.05.199w. Epub 2010 May 20.


Background: To study the effect (s) of recombinant human Epidermal Growth Factor (rhEGF) on naproxen induced gastric ulcer in Wistar NIN rats.

Methods: Male Wistar NIN rats were randomly divided into six experimental groups: Group I - Control, Group II - Naproxen treated, Group III - Naproxen with rhEGF/7 days, Group IV - Naproxen without rhEGF/7 days, Group V - Naproxen with rhEGF/14 days, and Group VI - Naproxen without rhEGF/14 days. Gastric ulcer was induced with naproxen at a concentration of 80 mg/kg by oral administration. After 24 hours of induction of ulcer, rhEGF treatment was started at a concentration of 100 µg/kg. Ulcer presence and healing were confirmed by histopathology study and molecular markers.

Results: Naproxen per se induced gastric antral ulcers in Wistar NIN rats. Compared with control rats, naproxen induced rats had increased lipid peroxide content in serum. Subsequent decrease in lipid peroxide was observed in rhEGF treated groups. Treatment with rhEGF significantly resulted in healing of the ulcers, which was evident by 7 days of rhEGF treatment with total healing seen by 14 days. Significant increase in immunoreactivity for Cox-2 was observed when compared to control groups, whereas less immunoreactivity of Cox-2 was observed in rhEGF treated group. Compared with control group, naproxen induced group exhibited more gene expression of both Cox-2 and TGF beta while gene expression of Cox-2 and TGF beta in rhEGF group was comparable to control group.

Conclusions: The beneficial effects of rhEGF in the management of ulcer healing can be understood. Oral rhEGF can promote healing of the rats with gastric ulcer by stimulating Cox-2 and TGF-beta expression.

Keywords: Gastric-antral ulcer; Healing; NSAIDs; Naproxen; WNIN rats; rhEGF.