Gastrointestinal and hepatic toxicity of selective and non-selective cyclooxygenase-2 inhibitors in pregnant and non-pregnant rats.

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Burdan F, Szumilo J, Klepacz R, Dudka J, Korobowicz A, Tokarska E, Cendrowska-Pinkosz M, Madej B, Klepacz L

Gastrointestinal and hepatic toxicity of selective and non-selective cyclooxygenase-2 inhibitors in pregnant and non-pregnant rats.

Pharmacol Res. 2004 Nov;50(5):533-43.

PubMed ID

15458776 [ View in PubMed

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Abstract

The aim of the study was to evaluate the toxicity of non-selective (tolmetin, ibuprofen and piroxicam) and selective (DFU) cyclooxygenase-2 inhibitors on pregnant and non-pregnant rats. The drugs were administered orally once (DFU, piroxicam) or three times (tolmetin, ibuprofen) a day from days 8 through 21 of gestation experiment in three doses. The initial dose was similar to the human antiinflammatory one and set as 8.5 mg/kg (tolmetin, ibuprofen), 0.3 mg/kg (piroxicam) and 0.2 mg/kg (DFU). The middle dose was increased 10 times and the highest one 100 times the initial dose. The highest dose for ibuprofen was set at 200mg/kg due to high mortality. On gestation/experimental day 21 animals were sacrificed, blood was collected and abdominal organs were taken for pathological examination. Activity of alanine and asparate aminotransferases and levels of total protein and urea were determined. Stomach, small and large intestines, and liver were grossly and histologically examined. Dose-dependent mortality, signs of gastrointestinal toxicity, and significant changes of biochemical parameters were found in groups exposed to non-selective COX inhibitors in both pregnant and non-pregnant rats. Mild regressive structural hepatic changes were observed. Significant decrease of protein level in non-pregnant rats treated with high DFU dose, and occasionally observed gastrointestinal changes were the only changes noted in groups exposed to the selective COX-2 inhibitor. Tolerability of non-selective COX inhibitors was lower in both pregnant and non-pregnant groups when compared with DFU. Insignificant mortality and histological changes were noted between pregnant and non-pregnant groups.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tolmetin	Prostaglandin G/H synthase 2	Protein	Humans	Yes	Inhibitor	Details