title: Preventive Effects of Tocotrienol on Stress-Induced Gastric Mucosal Lesions and Its Relation to Oxidative and Inflammatory Biomarkers.
abstract: This study aimed to investigate the possible gastroprotective effect of tocotrienol against water-immersion restraint stress (WIRS) induced gastric ulcers in rats by measuring its effect on gastric mucosal nitric oxide (NO), oxidative stress, and inflammatory biomarkers. 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) orally. After 28 days, rats from one control group and both treated groups were subjected to WIRS for 3.5 hours once. Malondialdehyde (MDA), NO content, and superoxide dismutase (SOD) activity were assayed in gastric tissue homogenates. Gastric tissue SOD, iNOS, TNF-α and IL1-β expression were measured. WIRS increased the gastric MDA, NO, and pro-inflammatory cytokines levels significantly when compared to the non-stressed control group. Administration of tocotrienol and omeprazole displayed significant protection against gastric ulcers induced by exposure to WIRS by correction of both ulcer score and MDA content. Tissue content of TNF-α and SOD activity were markedly reduced by the treatment with tocotrienol but not omeprazole. Tocotrienol significantly corrected nitrite to near normal levels and attenuated iNOS gene expression, which was upregulated in this ulcer model. In conclusion, oral supplementation with tocotrienol provides a gastroprotective effect in WIRS-induced ulcers. Gastroprotection is mediated through 1) free radical scavenging activity, 2) the increase in gastric mucosal antioxidant enzyme activity, 3) normalisation of gastric mucosal NO through reduction of iNOS expression, and 4) attenuation of inflammatory cytokines. In comparison to omeprazole, it exerts similar effectiveness but has a more diverse mechanism of protection, particularly through its effect on NO, SOD activity, and TNF-α.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Mohd Fahami
authors.initials: MF
authors.lastname: Nur Azlina
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Yusof
authors.initials: Y
authors.lastname: Kamisah
authors.affiliation: Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Kien Hui
authors.initials: KH
authors.lastname: Chua
authors.affiliation: College of Medicine, Umm Al Qura University, Makkah, Saudi Arabia.
authors.forename: Ibrahim Abdel Aziz
authors.initials: IA
authors.lastname: Ibrahim
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Hj Mohd Saad
authors.initials: HM
authors.lastname: Qodriyah
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects*; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009853:Omeprazole / Q000008:administration & dosage; D018384:Oxidative Stress; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects; D013276:Stomach Ulcer / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D024508:Tocotrienols / Q000008:administration & dosage / Q000494:pharmacology*; D016211:Transforming Growth Factor alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D053583:Interleukin-1beta; D024508:Tocotrienols; D016211:Transforming Growth Factor alpha; D009569:Nitric Oxide; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D009853:Omeprazole