Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2017; 23(32): 5887-5894
Published online Aug 28, 2017. doi: 10.3748/wjg.v23.i32.5887
Comparison between tocotrienol and omeprazole on gastric growth factors in stress-exposed rats
Mohd Fahami Nur Azlina, Hj Mohd Saad Qodriyah, Kien Hui Chua, Yusof Kamisah
Mohd Fahami Nur Azlina, Hj Mohd Saad Qodriyah, Yusof Kamisah, Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
Kien Hui Chua, Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
Author contributions: Nur Azlina MF, Qodriyah HMS, Chua KH and Kamisah Y designed the research; Nur Azlina MF performed the research and wrote the paper.
Supported by Universiti Kebangsaan Malaysia Research Fund, No. UKM-DLP-066-2011 and No. FF-032-2012.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Universiti Kebangsaan Malaysia (UKMAEC approval number: 354/2011).
Conflict-of-interest statement: The authors have no conflict of interests to declare.
Data sharing statement: No additional data is available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Mohd Fahami Nur Azlina, DVM, MMedSC, PhD, Associate Professor, Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia.
Telephone: +603-91459574 Fax: +603-91459547
Received: December 23, 2016
Peer-review started: December 28, 2016
First decision: April 21, 2017
Revised: May 8, 2017
Accepted: July 22, 2017
Article in press: July 24, 2017
Published online: August 28, 2017

To investigate and compare the effects of tocotrienol and omeprazole on gastric growth factors in rats exposed to water-immersion restraint stress (WIRS).


Twenty-eight male Wistar rats were randomly assigned to four groups of seven rats. The two control groups were administered vitamin-free palm oil (vehicle) and the two treatment groups were given omeprazole (20 mg/kg) or tocotrienol (60 mg/kg) by oral gavage. After 28 d of treatment, rats from one control group and both treated groups were subjected to WIRS one time for 3.5 h. Gastric lesions were measured and gastric tissues were obtained to measure vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor-alpha (TGF-α) mRNA expression.


Rats exposed to WIRS for 3.5 h demonstrated the presence of considerable ulcers in the form of gastric erosion. The lesion index in the stressed control (S) group was increased (P < 0.001) compared to the tocotrienol treated and omeprazole treated groups. Stress led to a decrease in gastric VEGF (P < 0.001), bFGF (P < 0.001) and TGF-α (P < 0.001) mRNA levels and caused an increase in EGF mRNA (P < 0.001) that was statistically significant compared to the non-stressed control group. Although both treatment agents exerted similar ulcer reducing ability, only treatment with tocotrienol led to increased expression of VEGF (P = 0.008), bFGF (P = 0.001) and TGF-α (P = 0.002) mRNA.


Tocotrienol provides gastroprotective effects in WIRS-induced ulcers. Compared to omeprazole, tocotrienol exerts a similar protective effect, albeit through multiple mechanisms of protection, particularly through up-regulation of growth factors that assist in repair of gastric tissue injuries.

Keywords: Tocotrienol, Omeprazole, Restraint-stress, Gastric ulcers, Growth factors

Core tip: During the process of ulcer healing, growth factors such as epidermal growth factor, transforming growth factor-alpha, basic fibroblast growth factor and vascular endothelial growth factor acts by activating the migration of cells from the edge of the ulcer and cell proliferation together with the formation of granulation tissue and angiogenesis. Rats exposed to stress develop gastric mucosal ulcers and changes in expression of these growth factors surrounding the ulcers had been reported. Tocotrienol effects on gastric mucosal growth factors were compared to those by omeprazole in this study. The findings suggest that in contrast with omeprazole, tocotrienol has a protective effect on the gastric mucosa through its effect on these growth factors.