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Drug Chem Toxicol. 2018 Nov 14:1-13. doi: 10.1080/01480545.2018.1530261. [Epub ahead of print]

Gastroprotective effects of oleuropein and thymol on indomethacin-induced gastric ulcer in Sprague-Dawley rats.

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a Department of Biology, Faculty of Science , Ataturk University , Erzurum , Turkey.
b Department of Biology , Erzincan University , Erzincan , Turkey.
c Department of Biochemistry, Faculty of Veterinary , Ataturk University , Erzurum , Turkey.
d Department of Pathology, Faculty of Veterinary , Ataturk University , Erzurum , Turkey.
e East Anatolian High Technology Research and Application Center (DAYTAM) , Ataturk University , Erzurum , Turkey.
f Department of Medical Laboratory, Techniques Vocational School of Health Services , Alparslan University , Mus , Turkey.
g Department of Molecular Biology and Genetics, Faculty of Science , Ataturk University , Erzurum , Turkey.


Ethnopharmacological studies demonstrated that thymol (Thym) and oleuropein (Ole) have therapeutic potential for gastric ulcers. The molecular mechanism underlying the gastroprotective effects of these compounds have not been elucidated yet especially for their individual and combination use at high dose. Therefore, this study was conducted to explore their gastroprotective mechanisms on indomethacin (Indo)-induced gastric ulcer model. Ole (50,100, 250, and 500 mg/kg) and Thym (50,100, 200, and 500 mg/kg) were orally administered to the rats 10 min before the induction of ulcer with Indo. The combination of 500 mg/kg doses of Ole and Thym were applied. The gastric mucosa was evaluated histopathologically. Moreover, TAC/TOS, tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), endothelial nitric oxide synthase (eNOS), and caspase-3 levels were assessed by ELISA and the caspase-3 and TNF-α expressions were quantified by qRT-PCR. Indo-induced histopathological changes while Ole and Thym pretreatment prevented these effects. Unlike the 500 mg/kg dose of Ole treatment, the 500 mg/kg dose of Thym administration enhanced these damages. The decreased TAC, PGE2 levels and increased TOS, eNOS, TNF-α, caspase-3 levels were obtained in Indo group. However, these changes were reversed by Ole and Thym groups except the 500 mg/kg dose of Thym and the combination treatment groups. Similar trends were observed in the caspase-3 and TNF-α expression levels. These results demonstrated that enhanced inflammation, oxidant/antioxidant imbalance, and apoptotic activities were occurred in Indo, 500 mg/kg dose of Thym and the combination treatment groups while not in the other groups. The findings demonstrated the gastroprotective ability of Ole and low doses of Thym in gastric ulcer models.


Apoptosis; cytokine; gastric ulcer; oleuropein; oxidative stress; thymol

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