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    STUDIA BIOLOGIA - Issue no. 2 / 2003  

  Abstract:  Structural and Ultrastructural Aspects of the Hepatotoxicity of Nurofen in White Wistar Rats. Hepatotoxicity represents one of the most frequently investigated side effects of the drugs because the liver is the most important organ implicated in the biotransformation, activation and elimination from the organism of the medicines, including Nurofen - an antiinflammatory product widely used in the therapy of many human diseases. The investigations reported here aimed at establishing the structural and ultrastructural changes induced in the liver of the white Wistar rat by a daily dose of 250 mg Nurofen/kg body weight, administered for 35 days. Our study showed that Nurofen had a moderate hepatotoxic effect, which increased progressively during the whole experimental period, but, fortunately, had no irreversible character, a natural recovery process being possible after the end of the treatment. By light microscopy studies, we could notice a fat degeneration of the hepatocytes, an obvious intracellular and intracanalicular stasis of the bile, the appearance of lymphohistiocyte infiltrations in the Kiernan spaces, and just a very discrete vascular congestion and blood stasis of the intralobular capillaries. Ultrastructurally, it could be observed that the hepatocytes were the most affected by the treatment, generally they having a cytoplasm full of many small lipid drops, or a few large drops of lipids. Besides, simultaneously, in many cells, a significant amount of glycogen appeared, which was spread in the whole cytoplasm. In some hepatocytes, number of the lysosomes and peroxisomes increased. The nuclei seemed to be sensitive to Nurofen, their chromatin appearing markedly condensed on the inner surface of the nuclear envelope (cortical hyperchromatosis). The mitochondria were moderately swollen, and had vacuolised and rarefied matrix and cristae. The smooth-surfaced endoplasmic reticulum had an abnormal, vesicular aspect. Also, a few number of hepatocytes could be noticed in different destructive stages, some of them being completely destroyed. Concerning the Ito cells, our investigations demonstrated that unlike hepatocytes they had no lipids in their cytoplasm. In addition, we could observe a serious perturbation of the bile transit, both in the cells and in the intralobular canaliculi, and, simultaneously, the microvilli in the lumina of some canaliculi disappeared. The destructive processes in the liver were correlated with a discrete increase of the phagocytic activity of the Kupffer cells, the cytoplasm of which contained a large amount of included materials. Except for a very discrete collagen proliferation in the Kiernan space, no other irreversible histopathological modification could be observed at the level of the liver of the treated white Wistar rats, a fact which explains the natural recovery of the liver after the end of Nurofen administration, without any hepatoprotective or hepatoregenerative treatment.  
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