Thymoquinone: Novel gastroprotective mechanisms.
Ample of evidence proved the gastroprotective effect of thymoquinone (TQ), the main constituent of Nigella sativa oil; however, the full mechanistic cassette on the gastric ulcer etiopathogenesis is not fully elucidated. The aim of the present work is to unveil some of the possible mechanisms. Animals were injected with vehicle, TQ (10 & 20mg/kg), omeprazole (10 & 20mg/kg) or their combination (10mg/kg). Thirty minutes later, pyloric ligation was carried out and followed consequently with ischemia for another 30min, abided by reperfusion for 120min. The ischemia/reperfusion insult increased the gastric acid secretion, acid output, and pepsin, as well as the gastric mucosal content/activity of lipid peroxide, proton pump and myeloperoxidase, along with ulcer index. However, content/activity of gastric mucin, reduced glutathione, total nitric oxide, and superoxide dismutase were decreased. TQ, especially the high dose level, corrected the altered parameters in a comparable manner to that of the reference drug used, omeprazole. In addition, when the low doses were combined they add to each other to reach the effect of the high dose of either drug. These results showed that apart from its known antioxidant properties, TQ has novel gastroprotective mechanisms via inhibiting proton pump, acid secretion and neutrophil infiltration, while enhancing mucin secretion, and nitric oxide production.
Department of Pharmacology & Toxicology, October University, Egypt.
Mahmoud-Awny
MA
Magdy
El-Abhar
el-A
Hanan
El-Maraghy
el-M
Nabila
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology*; D019610:Cytoprotection; D004195:Disease Models, Animal; D005744:Gastric Acid / Q000378:metabolism; D005752:Gastric Mucins / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009569:Nitric Oxide; D009853:Omeprazole / Q000494:pharmacology; D010434:Pepsin A / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D013276:Stomach Ulcer / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D000897:Anti-Ulcer Agents; D000975:Antioxidants; D016227:Benzoquinones; D005752:Gastric Mucins; D008054:Lipid Peroxides; D054328:Proton Pump Inhibitors; D009569:Nitric Oxide; D009195:Peroxidase; D013482:Superoxide Dismutase; D010434:Pepsin A; D017506:H(+)-K(+)-Exchanging ATPase; D005978:Glutathione; D009853:Omeprazole; C003466:thymoquinone