Light and Electron Microscopic Study on the Effect of Different Forms of Allopurinol on the Kidney and Liver of Adult Male Albino Rat

BACKGROUND: Allopurinol is used in the treatment of gout, leishmaniasis, renal stone formation and in prophylaxis of hyperuricemia and its compilations associated with radiation therapy. Allopurinol is associated with multiple side effects in certain cases which include glomerulonephritis, nephritis, elevated hepatic enzymes, hepatic necrosis, leucopoenia, purpura and allergic diseases. Little researches showed that a steep dose-response relationship exists between allopurinol and its side effects. Some of these researches on the microcapsulation of allopurinol, which can reduce its side effects to a great extend. The aim of the present study was to investigate and compare the effects of sustained release microcapsule, no uric allopurinol and pure allopurinol on the kidney and liver of adult male albino rats. MATERIAL AND METHODS: The present study was conducted on 40 adult male albino rats of Sprague-Dawley strain (from Assiut University animal house). The rats were randomly classified into four groups (ten rats each). The control group, rats of which were left in animal house without any treatment and received vehicle only. The three treated groups received three different forms of allopurinol at dose 25 mg/kg of body weight daily for 14 consecutive days. Group II (the sustained release allopurinol microcapsule group) rats of which were given the allopurinol microcapsule suspension which proved sustained release. Group III (the No-Uric group) rats of which were given no-uric suspension. Group VI (the pure allopurinol group) rats of which were given pure allopurinol suspension. Both kidneys and liver of the four groups were removed from the animals and processed for routine histological and electron microscopic examination. FINDINGS: Kidney and liver of group II (the sustained release allopurinol microcapsule group) is more or less similar to the control group. In group III (the No-Uric group) and group IV (the pure allopurinol group) the glomerular space is significantly dilated, the proximal convoluted tubules are significantly reduced in their epithelial height and areas of hemorrhage observed between the tubules and deposits inside the loop of Henle. The electron microscopic picture of the glomeruli shows partial thickening of the glomerular basement membrane, disturbed capillary endothelium, irregularity of the minor processes of the podocytes and areas of glomerular sclerosis. The proximal and distal convoluted tubules shows cytoplasmic vaculation, cytoplasmic dense bodies, degenerated mitochondria and decrease basal enfolding. The proximal convoluted tubules shows destruction of the microvilli. The liver of group III (the No-Uric group) and group IV (the pure allopurinol group) shows areas of hemorrhage both in the central part of the hepatic lobule and on the peripheral part. The electron microscopic picture of the hepatocytes show vaculated cytoplasm, necrotic changes and the cord pattern is disturbed. The electron microscopic picture of the hepatocytes show marked reduction of the cytoplasmic organelles, degenerative changes in the mitochondria and little amount of rough endoplasmic reticulum. The nucleus is shrunken, little chromatin material and the nuclear membrane is irregular. CONCLUSION: the sustained release microcapsule allopurinol may lead to prolonged activity with avoidance of renal and hepatic side effects of frequent administration of allopurinol. These results may have clinical significance in the prevention of some side effects of allopurinol on kidney and liver. [Ashraf H. Abd-Elhakem. Light and Electron Microscopic Study on the Effect of Different Forms of Allopurinol on the Kidney and Liver of Adult Male Albino Rat. Life Sci J 2012; 9(3): 1286-1295]. (ISSN: 1097-8135). http://www.lifesciencesite.com. 184