side effects of the nonsteroidal anti-inflammatory drug [NSAID] ketoprofen on histological and ultrastructural aspects of the kidneys of albino rats

ABSTRACT

The present work deals with the effect of the therapeutic dose of the nonsteroidal anti-inflammatory drug, ketoprofen on the microscopic structure of the kidney of the albino rat. The present study also sheds light on the risk of using over-dosage either by mistake or in an unwise attempt at quick relieving the body pain. The intramuscular therapeutic dose of ketoprofen to albino rat was calculated and was found to equal 13.5 mg /kg body weight. Fifty adult male albino rats, Rattus norvegicus were used in the present study. The rats were equally allocated to five groups, each of 10 rats. Rats of the first group were kept as control. Rats of the second and third groups were injected daily with the therapeutic dose of ketoprofen for four and eight successive weeks respectively. Rats of the fourth and fifth groups were injected daily with double the therapeutic dose of ketoprofen for four and eight successive weeks respectively. In rats given the therapeutic dose of ketoprofen daily for four weeks and sacrificed 24 hours after the last dose, light microscope examination showed that Malpighian corpuscles and the kidney tubules revealed signs of degeneration. In rats given the therapeutic dose of ketoprofen daily for eight weeks the histological changes were in progression. A few numbers of glomeruli were increasingly congested and shrunken into dense masses of unrecognized structural details. The luminal borders of the cells lining the proximal convoluted tubules together with their microvilli were damaged. The electron micrographs of ultrathin sections of kidneys of rats given the therapeutic dose of ketoprofen daily for eight weeks showed that the glomerular capillaries were disorganized and occasionally their lining endothelium showed degeneration. The podocytes showed deteriorated and rarefied cytoplasm; and their primary processes were fragmented. Also, the foot processes appeared occasionally broad. In some cells of proximal convoluted tubules the microvilli completely disappeared. Occasionally, these cells gave broad blebs into the tubule lumen which became almost obliterated. The cytoplasm of few cells lining the distal convoluted tubules became moderately rarefied and vacuolated. In animals given double the therapeutic dose for four weeks many kidney glomeruli were fragmented and showed marked congestion and increased mesangium. The parietal walls of Bowman's capsules were damaged. The kidney tubules showed generalized hyalinization. A few numbers of t he tubule lining cells displayed pyknotic nuclei; some nuclei were karyolysed and even vanished. In animals given daily double the therapeutic dose of ketoprofen for eight successive weeks, the glomeruli were sclerotic and necrotic and the kidney tubules showed generalized hyalinization. In EM micrographs of kidney ultrathin sections, the configuration of the primary processes and the pedicels was greatly interrupted and disorganized. The capillary endothelium displayed signs of degeneration and disarray. The capillary basement membrane of the glomeruli exhibited regional attenuation or deformity. In some lining cells of the distal convoluted tubules, the cell organelles including mitochondria and lysosomes were noticeably electron dense, whereas the Golgi apparatus as well as the endoplasmic reticulum elements was degenerated