Comparative effects of fenclorac and indomethacin on gastrointestinal blood loss in the rat

Smyth, Robert D.; Mathur, Pershotam P.; Procaccini, Robert L.; Carr, Gary S.; Reavey-Cantwell, Nelson H.

doi:10.1016/0041-008x(76)90182-4

Cited by 7 publications

(1 citation statement)

References 16 publications

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“…Methodology for assessing G. I. bleeding in rats involves the measurement of blood loss either by counting the 51Cr-RBC content [2,3] or by measuring the amount of hemoglobin [4] found in feces. Alternatively intravenous injection 56FEC13 can be used to label the hemoglobin [4,5].…”

Section: Discussionmentioning

confidence: 99%

Assessment of gastric bleeding in rats: Effects of cyclooxygenase inhibitors and 16,16-dimethyl prostaglandin E2 on gastric bleeding

et al. 1987

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Gastric bleeding caused by cyclooxygenase inhibitors has been assessed by a novel method. Rats are adapted to a strict light-dark cycle with limited access to food to reduce the stress associated with starvation. Such animals are then labeled with 51Cr-red blood cells from donor animals and dosed with the compound under evaluation. After 24 hr. animals are sacrificed and the amount of blood that has accumulated in the lumen of the cecum is quantitated. The potency of cyclooxygenase inhibitors in this assay to cause gastric bleeding is as follows: indomethacin greater than piroxicam greater than naproxen greater than ibuprofen greater than diflunisal which is similar to their antiinflammatory potency in the rat. In addition, the protective activity of PGE2 on indomethacin-induced gastric bleeding is clearly shown by this method.

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Section: Discussionmentioning

confidence: 99%

Assessment of gastric bleeding in rats: Effects of cyclooxygenase inhibitors and 16,16-dimethyl prostaglandin E2 on gastric bleeding

et al. 1987

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The inhibition of prostaglandin synthetase in vivo by nonsteroidal anti-inflammatory agents

Mathur¹,

Riley²,

Richardson³

et al. 1977

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The effects of two nonsteroidal anti-inflammatory compounds, fenclorac and indomethacin, on arachidonate and prostaglandins (PG) E1- and E2-induced vasodepressor responses were determined in the spontaneously hypertensive male rat. A 0.4 to 2 mg/kg intravenous dose of fenclorac blocked the arachidonate-induced vasodepressor response and had no effect on PGE1- and E2-induced hypotension. Similar responses were observed after indomethacin. These results were indicative of in vivo inhibition of PG synthetase by fenclorac and indomethacin. Administration of propranolol did not alter the arachidonate or PG responses; regitine reduced the arachidonate and PG response, suggesting that alpha-adrengergic receptors in vascular smooth muscle may play a role in the prostaglandin-induced hypotension.

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Comparative studies on the gastrointestinal lesions caused by several nonsteroidal anti-inflammatory agents in rats

et al. 1987

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The gastrointestinal toxicity of a single oral administration of five nonsteroidal anti-inflammatory agents (NSAIDs) to rats was compared, by a method using 51Cr-labeled red blood cells (RBC), and by macroscopic and microscopic examination. From the profile of gastrointestinal bleeding, the NSAIDs could be divided into a group consisting of aspirin (ASA), oxaprozin (OXP) and 2-[4-(3-methyl-2-butenyl)phenyl]propionic acid (TA), which caused only a transient increase in fecal blood loss based on a gastric lesion, and another group including indomethacin (IM) and ibuprofen (IP), which produced a biphasic increase in the blood loss. The initial phase was caused not only by a gastric lesion but also an intestinal lesion, and the secondary phase originated only in the intestinal lesion. The order of potency causing blood loss was IM much greater than IP greater than ASA much greater than TA greater than OXP. The safety ratio of OXP and TA was shown to be more favorable than that of the other three drugs.

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Comparative effects of fenclorac and indomethacin on gastrointestinal blood loss in the rat

Cited by 7 publications

References 16 publications

Assessment of gastric bleeding in rats: Effects of cyclooxygenase inhibitors and 16,16-dimethyl prostaglandin E2 on gastric bleeding

Assessment of gastric bleeding in rats: Effects of cyclooxygenase inhibitors and 16,16-dimethyl prostaglandin E2 on gastric bleeding

The inhibition of prostaglandin synthetase in vivo by nonsteroidal anti-inflammatory agents

Comparative studies on the gastrointestinal lesions caused by several nonsteroidal anti-inflammatory agents in rats

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