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NSAID gastropathy: prevention by celery seed extracts in disease-stressed rats

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Previous studies showed that some anti-inflammatory celery seed extracts (CSEs) were not gastrotoxic, in contrast to many OTC NSAIDs, when dosed to arthritic rats. The present investigation was designed to quantify the potential activity of CSEs against NSAID injury in rats with severe acute or chronic inflammation and to define the possible relationship of this to effects on mucosal prostaglandin production. Oral doses of alcoholic (A-CSE) (150-300 mg/kg) and supercritical fluid (S-CSE)(20-50 mg/kg) extracts of seeds of wild celery Apium graveolens from north India (Beagle Int. Nerang, Qld.) profoundly suppressed gastric injury elicited in disease-stressed female rats (Wistar, DA) with (a) chronic arthritic inflammation or (b) severe acute inflammation (from oleyl alcohol, 0.1 ml in tail base), fasted overnight and then dosed either (i) orally with ibuprofen (50 mg/kg), sodium naproxen (27.5 mg/kg), ketoprofen (5 mg/kg) or acidic ethanol (150 mg/kg); or (ii) parenterally with piroxicam (5 mg/kg) or nabumetone (100 mg/kg). By contrast several conventional gastroprotectants, e.g. sucralfate, cimetidine, bismuth salts, all given orally were ineffective in preventing gastric injury from parenteral piroxicam. Gastroprotection by CSEs was not over-ridden by co-dosing with isotonic HCl. Most other celery seed 'oils' were ineffective in these assays. A-CSE was found to have marked inhibitory effects on PGE2 production by porcine gastric (fundic) mucosal explants in organ culture. Quercetin and mycrecetin which are reported components of some CSEs also inhibited PGE2 production in concentrations of 10 μM, whereas limonene, another reported component of CSEs had little effect at the same concentration. These results suggest that gastroprotective effects of CSEs are probably mediated through non-prostaglandin mechanisms.

Affiliations: 1: Therapeutics Research Unit, Department of Medicine University of Queensland, Princess Alexandra Hospital, Woolloongabba, Qld, Australia 4102; 2: Biomedical Research Centre and Division of Biomedical Sciences, Sheffield Hallam University, Howard Street, Sheffield, S1 1WB, UK


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