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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 (Gp 1), 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 (GP1a and GPIb ) 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 2’ week of administration in female and from the 3rd week in males.
Similar hepatic as well as intestinal lesions were seen in a male and female tieated 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 2 week of administration.