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Diclofenac-aglycone (DCF-AG) is a good substrate for Escherichia coli beta-D-glucuronidase. A novel bacteria-specific beta-glucuronidase inhibitor (Inhibitor-1). It inhibited DCF-AG hydrolysis in vitro.
We hypothesized that inhibiting bacterial beta-glucuronidase reduces aglycone exposure. This could alleviate enteropathy. C57BL/6J mice received an ulcerogenic Diclofenac (DCF) dose (60 mg/kg i.p.). Some had oral pretreatment with Inhibitor-1 (10 µg per mouse, b.i.d.). DCF alone caused large ulcers in the small intestine. It doubled intestinal permeability to fluorescein isothiocyanate-dextran. Inhibitor-1 reduced mucosal injury…