الامراضية السمية لنابروكسين الصوديوم في الجرذان البيضاء مع الكيتوبروفين كعامل تحكم ايجابي == Toxicological Pathology of Naproxen Sodium In White Laboratory Sprague Dawley Rats (Rattus Rattus) With Ketoprofen As Positive Control
Author name:
ثائر علي محسن
Supervisor name:
زينب وحيد خضير | صالح كاظم مجيد
General topic:
Veterinary Medicine
Specific topic:
Veterinary Medicine
Degree:
Master
University:
University Of Basrah - College Of Veterinary Medicine
Language:
English
University location:
Basrah
First pages:
21T518 - p.pdf
Abstract:
ان الغرض من الدراسة هو تحديد السمية المرضية الدوائية لنابروكسين الصوديوم (كعامل مضاد التهاب غير استيرويدي) في الجرذان البيضاء، مع الكيتوبروفين كعامل تحكم ايجابي. لانها ذات فائدة على نطاق واسع في الحيوان والانسان، لتلقي العلاج الميداني، ومعرفة العلامات الس | The purposes of study are : first, to determine the toxicity and pathogenesis of naproxen sodium [as non - steroidal anti - inflammatory agent(NSAIDs)] in white rats in comparison with ketoprofen as positive control, as they are of wide use in animal and human, for treatment of variable disease; and knowledge of the clinical signs, macroscopic changes and microscopic changes by toxic dose of naproxen, second to observe note - 1 the histological changes in comparison with the control group (as untreated group), and note - 2 to examine the biochemical parameters in response to naproxen treatment, note - 3 where naproxen is (NSAID) with analgesic and antipyretic properties. In the present study, white rats are used. Divided into five groups each group contain 12 rats; these group divided into the following manner : The first group - C, representing untreated group has been treated with normal saline only; the second group - L, representing the low dose which has received (5mg/kg B.W) of naproxen sodium, while the third group - I is the intermediate dose, which has received (10mg/kg B.W); the fourth group - H, representing the high dose, that has received (20mg/kg B.W), and finally the fifth group, representing the positive control group, has received(4mg/kg B.W of ketoprofen). The method of dosing these animals are by oral gavage which continues for three months. All the animal groups have been put in the same conditions of temperature and humidity. This study shows that the treatment with naproxen sodium has led to significant gradually increase in the body weight of both high dose and intermediate dose groups in early treatment period in comparison with the control group. In contrast, the animals which have received low dose of naproxen sodium show only minimal and gradual increase in their body weight in comparison with the intermediate and high dose. As well as there has been noticeable little increase and decrease in some value of liver and kidney enzymes concentrations(AST, ALT, ALK, Urea/Cr as treated with naproxen and positive control of ketoprofen). The study also showed that the treatment with naproxen sodium had led to clinical findings include uterine hemorrhage and still birth which specially occurs in the last period of pregnancy. Infections happen in some regions of body forming abscess in the subcutaneous tissue of neck, leg, cheek. The macroscopic findings include pallor of liver and Abscess of the liver and kidney, also there is increase in size of the spleen as a result of congestion of the splenic red pulp and minimal changes of the mucosa of the stomach. Moreover the microscopic findings include minimal hepatic periportal fibrosis , moderate diffuse vacuolation of hepatocytes, area of vacuolated degenerative centrilobular hepatocyte arround the central vein and subcapsular infiltration of inflammatory cells. There was necrosis of renal cortical tubules and atrophy of glommeruli, vacuolation of mesenchymal glomerulular cells , dilated vacuolated cortical tubules, some with degeneration and loss of epithelial in lumen and degenerative necrotic tubules. In addition there is degenerative and vacuolative changes of myocardial muscle cells, and atrophy of myocardial muscle cells; and there was an evidence of interstitial edema. as well as there is atrophy of white pulp lymphoid tissue and congested of red pulp, also there was increase cellularity of red pulp(present of macrophage cells in red pulp). Furthermore,the present study exposes that the treatment with naproxen sodium would lead to other histo - pathological changes in the stomach and small intestine include vacuolation of mucosal epithelial cells of the stomach and inflammatory cells in the serosa with noticeable presence of prominant ganglion cells in the outer zone of muscularis externa and degeneration of mucosal lining and mucosal glands in the lamina propria of stomach(glandular region). In addition there have been vacuolation and degeneration of mucosal epithelial lining of small intestine , ulceration of the mucosa in the small intestine , increase in length of the villi and infiltration of inflammatory cells in lamina properia and inflammatory cells in the serosa and vacuolation of muscularis externa. In the colon there is vacuolation (prominent mucous gland) and mix of inflammatory cells infiltration, vacuolation (increase mucous gland) and a few mononuclear cells in the lamina propria and there was increase minimal fibrosis.Either in the uterus there was thicken fibrotic lamina propria and few endometrial gland. Finally the pathological changes that have been found for high dose group of naproxen prove to be more severe than both the intermediate and low dose groups.
