title: Protective activity of crocin against indomethacin-induced gastric lesions in rats.
abstract: The present study was designed to elucidate the mechanism(s) of the gastro-protective effect of crocin against indomethacin-induced gastric lesions. Crocin or pantoprazole was administered to rats 30 min before indomethacin. Five hours later, the animals were killed and their stomachs were removed and examined macroscopically. Samples of gastric mucosa were collected for microscopic evaluation, mRNA expression of caspase-3, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 was quantified by RT-PCR, and protein levels of COX-1, COX-2, iNOS and caspase-3 were assessed by Western blotting. The pH, volume of gastric effluent and antioxidant activity were measured in 5 separate groups of rats following pylorus ligation. Indomethacin induced significant increases in mRNA and protein expression of iNOS and caspase-3 and increased MDA levels, and reduced the pH of the gastric effluent and protein and mRNA expression of COX-2 and protein expression of COX-1 and mucus content associated with gastric ulceration. Crocin and pantoprazole significantly inhibited mRNA and protein expression of iNOS, caspase-3 and MDA, and reduced mucus content induced by indomethacin. However, unlike pantoprazole, crocin failed to increase COX-1 and pH, but had variable increasing effects on mRNA and protein expression of COX-2. Macroscopic and microscopic observations showed that mucosal erosions induced by indomethacin were significantly inhibited by pantoprazole and crocin. These findings suggest that crocin exerts its gastro-protective effects mainly by inhibition of MDA, reduction in iNOS and caspase-3, and inhibition of the reduction in mucus content induced by indomethacin. Crocin is a novel agent that has potential in the prevention of ulceration induced by NSAIDs.
authors.affiliation: Physiology Research Center (PRC), Research center for Infectious Diseases of Digestive System and Department of Physiology, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. alimard77@gmail.com.
authors.forename: Seyyed Ali
authors.initials: SA
authors.lastname: Mard
authors.affiliation: Toxicology Research Center and Department of Pharmacology, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Mohammad Hasan
authors.initials: MH
authors.lastname: Pipelzadeh
authors.affiliation: Research center for Infectious Diseases of Digestive System and Department of Virology, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Teimoori
authors.affiliation: Research center for Infectious Diseases of Digestive System and Department of Virology, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Niloofar
authors.initials: N
authors.lastname: Neisi
authors.affiliation: Physiology Research Center (PRC), Research center for Infectious Diseases of Digestive System and Department of Physiology, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Simindokht
authors.initials: S
authors.lastname: Mojahedin
authors.affiliation: Physiology Research Center (PRC), Research center for Infectious Diseases of Digestive System and Department of Physiology, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Maryam Zolfaghari Sabzeh
authors.initials: MZ
authors.lastname: Khani
authors.affiliation: Physiology Research Center (PRC), Research center for Infectious Diseases of Digestive System and Department of Physiology, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Iraj
authors.initials: I
authors.lastname: Ahmadi
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002338:Carotenoids / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D007213:Indomethacin / Q000009:adverse effects*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D000077402:Pantoprazole; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000188:drug therapy*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008565:Membrane Proteins; D012333:RNA, Messenger; D002338:Carotenoids; C029036:crocin; D000077402:Pantoprazole; D052247:Nitric Oxide Synthase Type II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; D053148:Caspase 3; D007213:Indomethacin
keywords: Anti-apoptotic; COX-1; COX-2; Caspase-3; Crocin; Pantoprazole; Rat; iNOS