الفهرس 
Aim of WorkOnly 14 pages are availabe for public view
 |  | from | 207 |  |  |
| | | from | 207 | | |
Abstract
The newly developed and rapidly growing concept of presence of two isoforms of cyclooxygenase (COX) enzyme open new area for researches in the field ofNSAIDs which have their main mechanism of action through inhibition of COX enzyme. The partof main interest is those agents with relative selectivity on COX4I isoform to get potent . antiinflammatory activity with fewer side effects or less liability for interaction with other drugs. The practical part of the present work investigated the effect of NSAIDs on the response to diuretics in rats and was designed as a comparative study of the effect of different NSAIDs which are either selective COX-II inhibitor (meloxicam) or non selective COX inhibitors with preferentially COX-I inhibitory activity (indomethacin) or with equal inhibitory activity on both enzymes (diclofenac) on the diuretic response to the most commonly used two diuretic groups namely loop diuretics (frusemide) and thiazide diuretics (hydrochloro¬thiazide). PGE2 urinary excretion was measured as a trial to find its role in such possible interaction. 360 males albino rats were divided into 12 groups the control group, the diuretic treated group (frusemide or hydrochlorothiazide), the NSAIDs treated groups (indomethacin, diclofenac, or meloxicam) and the combined treatment groups (frusemide in rat groups pretreated with either indomethacin, diclofenac or meloxicam and hydrochlorothiazide in rat groups pretreated with either indomethacin, diclofenac or meloxicam). Each group was subdivided into subgroups of four rats that were caged in special metabolic cages, designed for urine collection. The pooled urine collected during 5 hours from each four rats was considered as one sample. The volume of collected urine from each subgroup was measured and samples were analyzed for estimation of concentrations of sodium, potassium, chloride, phosphate and PGE2 metabolite and the total urinary 5 hours excretion was calculated for each. Oral administration of indomethacin (1.6 mg/kg/day) or diclofenac (OJ mg/kg/day) for seven days produced significant decrease’ in the total 5 hours urine volume, sodium, potassium and chloride excretion in rats as compared with the saline treated group. On the other hand, meloxicam in a dose (0.14 mg/kg/day) for seven days produced a non significant change . Indomethacin or diclofenac produced significant decrease’ in the urinary excretion ofPGE2 metabolite as compared with the saline treated group. Meanwhile, meloxicam administration did not decrease urinary PGE2 metabolite excretion significantly as compared with the saline treated group. In this work, pretreatment with indomethacin or dic10fenac for seven days lead to a significant reduction.