SUB-ACUTE TOXICITY STUDY OF DICLOFENAC SODIUM ON WISTAR RATS
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Date
2007
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AAU, Anand
Abstract
The present study was conducted on 5-8 weeks old Wistar rats. Forty eight Wistar rats divided in to four different groups with equal numbers of male and female. Group I was severed as vehicle control. Group II, III and IV were administered with 4, 8 and 12 mg/kg of Diclofenac sodium per kg body weight daily once oral intubation was carried out for 28 days. All the animals were monitor for any observable toxic symptoms and mortality throughout the experimental period. All the animals were weighed weekly to monitor body weight gain. The food consumption was also measured once a week. After completion of 28 days of administration of Diclofenac sodium the blood samples were collected through cardiac puncture for haematological and biochemical investigations. After terminal sacrifice all the animals were subjected to necropsy and organs like liver, kidneys, spleen, heart, stomach, small intestine and large intestine were collected for histopathological examinations. The relative organ weights of liver, kidneys, spleen and heart were calculated. The extent and severity of the observed symptoms varied according to dosage administered to the animals. The toxic symptoms observed in 8 mg/kg and 12 mg/kg dose groups were weakness, lethargy, pale mucous membrane and distended abdomen. The reduction in the body weight was observed in the animals of 8 mg/kg and 12 mg/kg dose group. There was significant reduction in the red blood corpuscles, pack cell volume, haemoglobin and mean corpuscular haemoglobin concentration, where as significant increase in absolute neutrophils and mean corpuscular volume in animals of 8 mg/kg and 12 mg/kg. No significant changes observed in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin in any of the dose group. The significant decrease in total protein, albumin, globulin, glucose and cholesterol and significant increase in urea, creatinine, uric acid and triglycerides was observed in 8 mg/kg and 12 mg/kg dose groups. The animals of 12 mg/kg dose group revealed significant increase in relative organ weights of liver, kidneys, spleen and heart. Gross postmortem changes observed in the animals of 12 mg/kg dose group were ascitis, peritonitis, erosion with or without ulcers in stomach, fibrinous adhesion of various part of small intestine with mesentery, spleen, liver and intestine it self with or without ulcer and erosion in lumen. Enlargement of spleen was the common findings in the animals of 12 mg/kg dose group. Microscopic changes observed in kidneys, stomach and small intestine of the animals from 8 mg/kg and 12 mg/kg dose groups were related to gross lesions, in dose dependent severity.
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VETERINARY PATHOLOGY, A STUDY