الفهرس 
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Abstract
The present work was performed in order to evaluate pathologically the suspected adverse effects following repeated therapeutic as well as double and triple therapeutic doses of doramectin on the liver and intestine of healthy guinea pigs.
A total number of 96 adult guinea pigs (48 males and 48 females) weighing 350 —450 g, were used. These guinea pigs were divided into 4 main groups:
Non-treated group (Gpl ), treated group with therapeutic dose (GP2), treated group with double therapeutic doses (GP3) and last group of treatment with triple therapeutic doses (Gp4)• Each of these 4 main groups were subdivided into 2 subgroups , (one consisted of 12 males and the other consisted of 12 females) and each are maintained in a
separate cages.
The doramectin was administered through intramuscular injection at three dose levels, 0.2, 0.4 and 0.6 mg/Kg bwt.
The animals in subgroups group 1 (GPia and GPII, ) not received any injections and remained as a control for other subgroups. The animals in each of the treated groups received a weekly single injection until the end of the experiment (6 weeks). So for example the sacrificed cases at the 6th week were received a total number of 6 injections
doses, one per each week.
Four animals (2 males and 2 females) of each main groups were weekly sacrificed for postmortem examination and tissue specimens were collected from the liver and small intestine (duodenum, jejunum and ileum) and subjected for the histopathologic studies.
The mostly detected gross lesions were seen in case of treatment with the level of 0.6 mg/Kg b.wt. The liver showed some discolourations of pale to grayish areas or sometimes other deep-brown congested areas from the second week of administration in female animals or from the last 3 weeks in male animals. Some signs of diarrhea with deep-brownish watery fecal matters were observed during the last 2 weeks of treatment in both
male and female animals of the same group.
On gross examination for the organs of treated male and female groups some changes were seen, especially in cases treated with the repeated triple therapeutic doses. The liver showed pale, grayish to deep brown discoloration which appeared early from the 2nd week of administration in female and from the 3”I week in males.
Similar hepatic as well as intestinal lesions were seen in a male and female treated guinea pigs, with exceptionally early and somewhat progressed lesions in females than males. In case of repeated administration of the therapeutic doses, mild lesions of hepatocytic vacuolations and congestion were seen in the liver, while in case of the double therapeutic doses some progressive lesions of congestion, hemorrhages, hepatocytic degenerations (Vacuolar and hydropic) and necrosis and mononuclear cell infiltrations and aggregations were sequentially seen from the 2nd week of administration. The various congested vasculatures of the liver in the present work appeared to contain excess of abnormal red blood cells with peripheral secretion or crenated cell membrane (Burr cells).
The intestinal tract of these treated groups with the double therapeutic doses wa also affected. Some non-specific changes of edema and congestion were seen in the mucosa of the jejunum from the 4th s
week, it was accompanied with duodenal changes of edema congestion, hemorrhages and hemosidrosis at the last weeks of the experiment.
Regarding to histopathologic findings in cases treated with triple therapeutic dos es
eneration of doramectin, in the present study, some more diffuse and advanced deg and e necrotizing hepatic lesions were seen, especially in the last weeks of the experiment. Th intestinal tract was also affected with some distribution of the lesions from the duodenu to the ileum. These intestinal lesions were variable from the degrees of edema m
congesti and hemosidrosis to the mononuclear cell infiltrations with degeneration and, necrosison
of the lining epithelium of the intestinal villi. In general, the obtained results about the adverse effect of repeated and overdoses of doramectin on the liver and intestinal mucosa of guinea pigs are mainly attribute related to the known high bioavaliability of doramectin, and its metabolites as wel d and
l as its long duration in body tissue
On other hand, the described lesions due to the repeated as well as duplicated as well therapeutic doses of doramectin were indicative for the necrotizing hepatic lesions as the intestinal lesions of toxicosis. That means although the known good antip
role of doramectin, it was found that it’s repeated and overdoses of administration may arasitic affecting the general health as well as feeding and digestive performance of treated animals, especially the females.