comparative study on liver toxicity profile of diclofenac sodium and piroxicam on rabbits

Aim of this study was to determine the clinical hepatotoxicity of diclofenac sodium and of piroxicam, and to evaluate whether these drugs could elicit liver cell destruction and anemia, and which drug is comparatively safer for prolong use. This study was conducted in the department of Pharmacology, Faculty of pharmacy, University of Karachi, Karachi. Duration of study was 30 days. Male 40 rabbits were equally divided into 4 groups, group A was served as control and the group B and C was diclofenac sodium [0.8mg/kg/day and 1.5 mg/kg/day], and group D was of piroxicam [0.31 mg/kg/day] treated. All the animals were caged in pair in an iron caged with free access to grass and hay of standard diet and tap water for a period of 30 days. Diclofenac sodium in 2 different doses 0.8mg/kg/day, 1.5 mg/kg/day and similarly Piroxicam [0.31mg/kg/day] dissolved in drinking water and was given orally for a period of 30 days. Control rabbits were given tap water. At the end of 30 days blood was collected through cardiac puncture from each rabbit and was analyzed to determine the levels of SGOT, SGPT, Bilirubin, ESR and Erythrocyte count. It was found that these drugs can induce severe hepatic damage but the ratio of liver toxicity is different, as evident by the elevation of serum aminotransferases, bilirubin and changes in hematological profile. The experimental results suggest that SGOT and SGPT levels were significantly increased in diclofenac sodium treated rabbits after 10 and 30 days [P> 0.01], while piroxicam treated rabbits showed significant result, [P<0.05] only after 30 days of treatment. The level of bilirubin was significantly increased in diclofenac sodium treated rabbits after 10 days and 30 days [P<0.01] and piroxicam also showed significant result [P<0.05] after 30 days treatment. Erythrocyte count decreased in both control and treated rabbits after 10 days but control results are not significant. After 30 days diclofenac sodium showed highly significant decrease in count of erythrocytes [P<0.01], but piroxicam showed less significant results [P<0.05]. E.S.R values significantly increased in diclofenac sodium and piroxicam treated rabbits after 10 days and 30 days. It can be concluded that diclofenac sodium and piroxicam both can play a role in inducing hepatocellular damage, but a greater increase in liver toxicity was seen in diclofenac sodium treated rabbits rather than piroxicam treated rabbits

Effect of piroxicam and zinc on morphological and histochemical changes in mice liver

To observe the morphological and histochemical findings, produced by piroxicam and zinc in mice liver and correlate with serum hepatic enzyme. For this experimental study 30 adult mice [25 -30 grams] were obtained from animal house of Jinnah Postgraduate Medical Center, and divided into three groups i.e. A, B and C. Group A served as control and received normal diet, Group B received piroxicam 0.3 mg /Kg body weight intraperitoneally and Group C 1mg/Kg body weight of zinc intraperitoneally and piroxicam in the same dose as group B. After completion of study [6 weeks] animals were scarified and their livers were removed and after processing paraffin section were made and stained with Haematoxylin and Eosin for histological and histochemical examinations and correlate with serum hepatic enzyme level. Haematoxylin and Eosin stained section of group A indicated the normal histology and morphometry, the group B showed distorted hepatic lobular architecture. Central vein and sinusoids was dilated and congested, kupfer cell prominent and pyknotic cells and mono nuclear infiltration were seen. Group C showed altered histological findings comparable to group A. The Histochemical findings of group B showed depletion in glycogen content marked fibrosis of reticulin fibres and increased deposition of calcium phosphate crystals. In group C effect of zinc improve glycogen content and reticulin fiber deposition and decreased deposition of alkaline phosphatase crystals. The serum enzyme level of Alkaline Phosphatase and Serum Gulutamin Phosphatase significantly increased in group B animals and less significantly increase in group C as compared to group B animals. It was concluded that piroxicam in therapeutic dose, was toxic and produced hepatic injury and zinc along with piroxicam improved the hepatic damage

Toxicological and inhibitory effect of Piroxicam on matrix Metalloproteinase expression in comparison with Diclofenac and Dexamethasone

Non-steroidal anti-inflammatory [NSAIDs] are used widely for musculoskeletal and other inflammatory conditions. In this study, the efficacy and toxic effects of Piroxicam was compared with Diclofenac and Dexamethasone in an in vitro fibrosarcoma cell culture [Wehi 964] model using cytotoxicity analysis and zymography assay. The concentration all the drugs ranged between 10 to 200 micro g/ml per ml of cell culture [20/000/well] and incubated overnight. The results showed that these drugs produced inhibitory effects on the expression of matrix Metalloproteinase [MMPs], in which Diclofenac was the most cytotoxic. The LD50 for Diclofenac was approximately 20 micro M compared to 80 micro M for Piroxicam and Dexamethasone, which had LD50 of 80 micro M. In addition, Diclofenac produced caused greater inhibitory effects on cell proliferation and cell death at higher concentration. These effects were found to be correlated with its inhibitory effect on MMPs expression. The above findings indicated that Piroxicam excess an inhibitory effect on expression of MMPs. Thus, this drug can be used in inflammatory conditions