Induced gastrointestinal tract (GIT) derangement following a long-term administration of a non-selective cyclooxygenase inhibitor – paracetamol in pregnant Sprague–Dawley rats

Abstract

There are two recognized isoforms of cyclooxygenase enzymes, the cyclooxygenase – 1 and cyclooxyg-enase – 2, the former is involved in the biosynthesis of prostaglandins, in organs where these eicosanoids play certain protective roles in the gastrointesional tract (GIT) and the kidney, it also enhances mucus secretions and acts as a house keeping enzyme expressed constitutively in most tissues of the body, while cyclooxygenase – 2 is the inducible form expressed in response to proinflammatory cytokines and growth factors, indicating a role in inflammation and growth and also maintains haemodynamics. In pregnant state, several drugs are used out of necessity, despite their reported toxicity. The clinical conditions often necessitating the use of non–selective cyclooxygenase inhibitors during pregnancy include hypertension, thromboembolism, hyperthyroid-ism, epilepsy, diabetes mellitus, preterm labour, arthritis, pain and fever, among others. The aim of this study was to investigate the induced gastrointestinal derangement following a long-term administration of paracetamol in pregnant Sprague–dawley rats. Twenty female adult Sprague–dawley rats weighing between 160g – 180g (as the beginning of the experiment) were used for the study. The animals were randomly divided into two groups (A and B) of ten rats each. Group A animals received distilled water orally and served as control. While paracetamol treated animals (group B) received doses of 7.3mg/kg/day respectively by gavage. The animal weights were monitored at an interval of three days before gestation to 13th day after parturition. The animals were allowed feed and water liberally. Drug administration commenced from 10th day of gestation to the end of parturition. On the 13th day after parturition the maternal rats were then sacrified for tissue processing. The results showed that the control animals had a normal architecture of the gastrointestinal tract. While the paracetamol treated animals showed a general derangement coupled with high degree inflammation of the stomach and intestinal lining, and a statistical significant weight loss (P<0.005) compared to the control animals. These findings reflect gastrointestinal tract impairment. We conclude that a long–term use of non-selective cyclooxygenase inhibitor – paracetamol in pregnant state has an erosive effect on the gastrointestinal tract and may possibly be the aftermath of gastrointestinal tract inflammation in women.

Keywords: cyclooxygenase inhibitor, paracetamol, gastrointestinal tract, inflammation, pregnancy

Nigerian Journal of Health and Biomedical Sciences Vol. 5(1) 2006: 51-56