الفهرس 
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Abstract
5-nitroimidazoles is one of the antiprotozoal agents that have been well established due its efficacy. Metronidazole is one of 5- nitroimadazole group which has found a wide variety range of application in therapeutics as in treatment of amoebiasis, giardiasis and trichomoniasis. Metronidazole requires treatment courses lasting several days during which many unpleasant side effects are developed that often leads to bad patient compliance and treatment failure.
Secnidazole is the first and most recent nitroimidazole proved to be effective in a single dose therapy of amoebiasis, giardiasis and trichomoniasis.
Recently, antioxidants especially vitamins have shown a great role in prevention and reversal of toxic effects of a wide variety of drugs and chemicals used. Vitamins as vitamin A and vitamin C are easily administered and have a variable sources whether natural or synthetic.
The present study was conducted to evaluate the acute and chronic toxic effects of metronidazole and secnidazole on the liver, kidney, blood leukocytes, chromosomal patterns, and immune system, as well as studying the role of vitamin A and vitamin C in reducing and/or preventing these effects.
The study was conducted on 420 adult albino rats which were divided into two main groups, the first main group consisted of 105 rats used to study the acute toxic effects and the second main group consisted
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of 315 rats used to evaluate the chronic toxic effects after one month, three months and after four week follow up.
The two main groups were subdivided into 7 groups: the first group used as control. The second group received MNZ (LD50 in acute study and 1/10 LD50 in chronic study). The third group received vitamin A in therapeutic dose with MNZ in a dose of (LD5o in acute study and 1/10 LD5o in chronic study). The fourth group received MNZ in dose as third group with vitamin C in therapeutic dose. The fifth group received SNZ in dose as MNZ in second group. The sixth group received SNZ in dose as MNZ in third group with vitamin A in therapeutic dose. The seventh group received SNZ in dose as MNZ in fourth group with vitamin C in therapeutic dose. Vitamins A and C were given four hours after MNZ ans SNZ administration.
Each rat was subjected to:
1-Biochemical determination of Liver functions (AST, ALT and Alk. Ph.)and kidney functions (BUN and S. creatinine).
2-Determination of total and differential leucocotyic counts.
3-Evaluation of mutagenic effects.
4-Histopathological examination of the liver and kidney.
5-Estimation of immunotoxic effects through PHA assay.
Regarding the biochemical changes, MNZ induced very high significant increase of all examined parameters of liver and kidney functions in all animals throughout all periods of the study especially acute toxicity and after 3 months of chronic toxicity. These effects were confirmed by the histopathological findings. The liver main lesions were hydropic degeneration, cellular infiltration, cloudy swelling and cellular degeneration. These changes began to be slightly reduced after four
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weeks follow up. The renal main lesions induced by MNZ were swelling of some tubules, compression of other tubules and areas of hemorrhage.
SNZ induced significant increase in all measured biochemical parameters of liver and kidney functions in acute toxicity study and after 3 months only. These effects were confirmed by the histopatholpgical findings. The liver showed fatty changes, cloudy swelling and cellular infiltration and the kidneys showed interstitial edema and cloudy swelling without areas of hemorrhage .
The incidence of structural and numerical chromosomal anomalies showed very highly significant increase in acute toxicity study and after three months in rats treated with MNZ but highly significant rise after one month and only significant rise after four weeks follow up.
Meanwhile SNZ induced significant increase in the frequency of chromosomal anomalies in acute toxicity study and after 3 months only, while after one month and after 4 weeks follow up it induced non significant increase in chromosomal anomalies.
The study of effects of MNZ and SNZ on total and differential leucocytic counts and immune system revealed non significant effects of both drugs.
Comparison between the effects of MNZ and SNZ indicates that SNZ is more safe than MNZ in acute toxicity and chronic toxicity studies.
As regard the protective role of vitamin .A and vitamin C, the results indicated that vitamin A had no protective action while vitamin C had a significant protective action against the acute and chronic toxic effects of both MNZ and SNZ.