The effects of daily oral administration for 2 and 4 weeks of 1/10 LD50 of Norfloxacin (NOR) (quinolone, broad spectrum antibiotic) on chromosomes, liver and kidney were studied in rats. After scarifice of rats, samples were taken from bone marrow, blood, liver and kidney to study the changes which occur in them. The study showed that NOR induced genotoxicity, hepatotoxicity and nephrotoxicity. The most frequent aberrations produced by NOR were chromatid gaps (CG), breaks (CB), separations(CS), fragments(CF), deletions (CD), ring chromosomes (RC) and polyploidies. Biochemical studies revealed elevation of ALT, AST, ALP, BIL, BUN and serum creatinine. All these finding increased after 2 weeks and markedly increased after 4 weeks of the drug administration indicating that toxic effects were time-dependent. The liver showed venous congestion and dilatation of the branches of portal vein in the portal tracts which were infiltrated by inflammatory cells. Some hepatocytes were vacuolated, other had small pyknotic nuclei and the blood sinusoids were dilated. Electron microscope (EM) examination showed that the cytoplasm of some hepatocytes was vacuolated and the mitochondria became more electron-dense. There was decrease of glycogen granules. The blood sinusoids became dilated with prominent von Kupffer cells. Also kidney by light microscopic (LM) examination showed that the proximal convoluted tubules were the most affected and their cells became swollen showing hydropic degeneration with some inflammatory cellular infiltrations and the lumen was oblitrated. Also signs of focal tubular necrosis with intra luminal necrotic epithelial debris were present. While EM examination revealed that the mitochondria became few and scattered and not confined within the basal infoldings. Some of them were degenerated with damage of outer and inner membranes and there were shortening of the foldings of basal membrane. The cytoplasm contained multiple vacuoles which were different in size and shape and some areas of cytoplasmic rarefaction were appeared. Also, the study showed that (NOR) toxicity was reversible after withdrawal of the drug. Thus, this antibiotic should be neither prescribed for long duration, nor for patients suffering from hepatic or renal disorders, except in highly indicated conditions with frequent monitoring of both liver and kidney function tests. |
