الفهرس 
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Abstract
In the present work, pathologic studies were done in order to study the adverse effects and tissue alterations in the adult male as well as female sex organs and also in the kidneys of healthy Guinea pigs after repeated administration of various dose levels of
doramectin.
During this study a total number of 96 adult guinea pigs (48 males and 48 females) weighing 350 — 450 g, were used. These guinea pigs were collected from private field with a known history of a previous treatment with any of avermectin therapy. The animals were grouped and housed in a separate metal cages and fed on standard pelleted rabbit food. Both food and water were supplied adlibitum.
Animals were grouped into 4 main groups, non-treated control group (Gpl ), treated group with therapeutic dose of dectomax (GP2) of 0.2 mg/Kg b.wt., treated group with double therapeutic doses (GP3) of 0.4 mg/kg b.wt and treated group with triple therapeutic doses (Gp4) of 0.6 mg/kg b.wt. Each of these four main groups were subdivided into 2 subgroups (one consisted of male and the other consisted of 12 female) which were maintained in two separate cages.
The treated animals given the dectomax as a weekly intramuscular single injections till the end of the experiment (6 weeks). The animals were kept under _observation for recording any clinical signs allover the experiment.
Four guinea pigs (2 males and 2 females) were taken weekly from each group , sacrificed and subjected for the postmortem examination during which any gross lesion were recorded. Tissue specimens were collected from the kidneys spleen, tests, epididymis. seminal vesicle and prostate glands and rendered for the following histopathologic studies.
Slight depression as well as recumbancy were seen in these treated cases with repeated triple therapeutic doses.
The macroscopic examination in male and female organs revealed presence of some non-specific lesions, especially during the last weeks of administration with triple therapeutic doses. The cut section in the renal cortex appeared with some pale, grayish to deep brown areas of discoloration.
The Other grossly examined organs of male (testes, epididymis, prostate gland and seminal vesicle) and female (Ovaries and uterus) showed some degrees of congestion of superficially located blood vessels.
In the examined organs of treated cases with therapeutic doses, no or sometimes minimal lesions (mild congestion in the kidneys and sometimes less active spermiogenesis in the testis) were seen.
The double therapeutic doses of doramectin in the present study revealed presence of more progressed lesions of nephrotoxicosis, especially in females. These lesions were seen in a sequential variable degrees of glomerular as well as intertubular congestion with mononuclear cell infiltrations and aggregations. The other detected lesions in sex organs were restricted on the congestion with interstitial edema in the prostate glands of males as well as in the uterus of females.
Sequential progressive lesions of nephropathy included degenerative changes in the tubular epithelium (granular , vacuolar and hydropic degeneration and hyaline cast formation) followed by tubular necrosis and accompanied with interstitial as well as periglomerular infiltration and aggregation of mononuclear cells in addition to the glomerular as well as inertubular congestion and hemorrhages.
The present findings for the histopathologic lesions in male sex organs appeared sequentially from the third week of administration. The findings were in the form of testicular degeneration and necrosis with the appearance of an excess of necrotic debris and immature spermatogonial cells in the lumina of the epididymis. Edema and congestion were also seen in the prostate gland. Some splenic lesions of depression of the lymphocytes with lymphocytic necrosis were also seen from the third week of administration.
The other obtained results for the histopathologic findings in female sex organs revealed also certain alterations from the 2”° week of administration of this triple therapeutic doses. Endometrial congested capillaries as well as edema were seen followed by the appearance of degeneration, necrosis and atrophy of the endometrial glands in the following weeks.
The ovaries were seen to be affected from the 4th week. Several degrees of follicular degeneration, necrosis and excess of atretic follicles with degenerated oocytes were seen. Similar splenic lesions were also seen in these female but appeared early from the 2” week of administration.
These results concluded that:
1-Minimal no adverse effect could be seen in case of repeated administration of the therapeutic doses.
2-The repeating as well as duplication for the therapeutic doses of doramectin usually leads to numerous adverse effects that may be lethal in case of prolonged administration.
3-Also these non-wide safety margins of administration lead to exact and dangerous effect on the reproductive performance of either treated male or female guinea pigs.