N M Davies1, B W Corrigan, F Jamali. 1. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Abstract
PURPOSE: To develop a non-invasive animal model suitable for studies of altered gastroduodenal (GD) permeability, which is suggested to indicate GD damage; to validate a low cost and convenient assay for sucrose in urine, a permeability marker of GD. METHODS: Control (n = 87) and treated male Sprague-Dawley rats were dosed orally with 1 g of sucrose. Urinary excretion of the sucrose (0-8 h) was measured indirectly by cleavage to glucose and subsequent measurement of glucose in urine using a calorimetric assay. Treated rats were administered single oral doses of 10 and 20 mg/kg indomethacin, or 42 mg/kg aspirin alone or with 0.5 mL 50% ethanol (n = 7 in each group). RESULTS: The assay was linear within the examined range of 10-100 ug/mL sucrose. The inter and intraday variations were 7.63% and 6.89%, respectively. The urinary excretion of sucrose was complete in 8 h. In control rats the urinary excretion of sucrose exhibited a left skewed frequency distribution curve with a mean of 0.6 +/- 0.14% of the dose excreted. All treatment, with the exception of 10 mg/kg indomethacin significantly increased the GD permeability. The GD effect was found to be dose dependent and parallels those reported for humans. CONCLUSIONS: The rat is a suitable model for studies of GD permeability. Combined use of sucrose and 51Cr-EDTA, a marker of intestinal permeability, allows for non-invasive examination of abnormalities of the entire gut. The sucrose assay is convenient and cost effective. The rat model may be useful in the preclinical screening of NSAID formulations and also in the detection of other GI abnormalities.
PURPOSE: To develop a non-invasive animal model suitable for studies of altered gastroduodenal (GD) permeability, which is suggested to indicate GD damage; to validate a low cost and convenient assay for sucrose in urine, a permeability marker of GD. METHODS: Control (n = 87) and treated male Sprague-Dawley rats were dosed orally with 1 g of sucrose. Urinary excretion of the sucrose (0-8 h) was measured indirectly by cleavage to glucose and subsequent measurement of glucose in urine using a calorimetric assay. Treated rats were administered single oral doses of 10 and 20 mg/kg indomethacin, or 42 mg/kg aspirin alone or with 0.5 mL 50% ethanol (n = 7 in each group). RESULTS: The assay was linear within the examined range of 10-100 ug/mL sucrose. The inter and intraday variations were 7.63% and 6.89%, respectively. The urinary excretion of sucrose was complete in 8 h. In control rats the urinary excretion of sucrose exhibited a left skewed frequency distribution curve with a mean of 0.6 +/- 0.14% of the dose excreted. All treatment, with the exception of 10 mg/kg indomethacin significantly increased the GD permeability. The GD effect was found to be dose dependent and parallels those reported for humans. CONCLUSIONS: The rat is a suitable model for studies of GD permeability. Combined use of sucrose and 51Cr-EDTA, a marker of intestinal permeability, allows for non-invasive examination of abnormalities of the entire gut. The sucrose assay is convenient and cost effective. The rat model may be useful in the preclinical screening of NSAID formulations and also in the detection of other GI abnormalities.
Authors: D W Kaufman; J P Kelly; J E Sheehan; A Laszlo; B E Wiholm; L Alfredsson; R S Koff; S Shapiro Journal: Clin Pharmacol Ther Date: 1993-04 Impact factor: 6.875
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