الفهرس 
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Abstract
Tulathromycin, the active ingredient of Draxxin®, is the first representative of a recent macrolide class, the triamilides, possessing physicochemical attributes that promote strong activity against gram-negative respiratory pathogens and extended pharmacokinetics in the lungs of cattle and swine.
The present work is carried out to study the effect of single and repeated subcutaneous administration of tulathromycin at a dose level 10 mg/kg B.wt. on the reproductive system of albino male rats. Moreover, some hematological, biochemical and histopathological changes were examined.
This study included fifty clinically healthy mature male albino rats weighing from 150 - 170 gm body weight each and about 5 months old. The animals were fed on bread, corn, carrots, lettuce and tap water ad.libitum.
The present study consists of two experiments. In the first experiment, rats were divided into two equal groups each of 15 animals. The first group received single subcutaneous injection of tulathromycin at a dose level of 10 mg/kg B.wt. The second group used as a control and injected intramuscularly with physiological saline solution at a dose of 2 ml/rat.
In the second experiment, rats were divided into two equal groups each of 10 animals. The first group received subcutaneous injection of tulathromycin at a dose level of 10 mg/kg B.wt. repeated once every week for eight successive weeks. The second group used as a control and injected intramuscularly with physiological saline solution at a dose of 2 ml/rat by the same manner.
Five rats from each group of the first experiment were sacrificed at 2nd, 4th and 8th weeks from the drug administration. Five rats from each group of the second experiment were sacrificed after two and four weeks from the drug administration.
The obtained results are summarized as follows:
I. Effect of tulathromycin on fertility of male rats:
1- Effect of tulathromycin on male reproductive organs weight:
a) Rats of first experiment: (single dose 10mg/kg B.wt.)
Rats treated with tulathromycin showed significant decrease in testes and epididymis weights at 2nd, 4th and 8th weeks from onset of drug administration as compared with control group. While there was no significant effect on accessory sex organs weight throughout periods of the First Experiment.
b) Rats of second experiment: (repeated dose 10mg/kg B.wt./week/8weeks)
There was a significant decrease in testes and epididymis weight at 2nd and 4th weeks from last drug administration as compared with control group. While there was no significant effect on accessory sex organs weight throughout periods of the Second Experiment.
2- Effect of tulathromycin on epididymal sperm chracters:
a) Rats of first experiment: (single dose 10mg/kg B.wt.)
There was non significant effect on sperm motility throughout periods of first experiment (at 2nd, 4th and 8th weeks from onset of drug administration) as compared with control group. While there was a significant increase in sperm abnormalities allover the periods of the first experiment (at 2nd, 4th and 8th weeks from onset of drug administration) as compared with control group.
b) Rats of second experiment: (repeated dose 10mg/kg B.wt./week/8weeks)
There was a significant decrease in sperm motility and count at 2nd and 4th weeks from last drug administration as compared with control group. Moreover, there was a significant increase in sperm abnormalities at 2nd and 4th weeks from last drug administration as compared with control group.
II- Effect of tulathromycin on hematological pictures:
a) Rats of First Experiment: (single dose 10mg/kg B.wt.)
There was a non significant effect on haemoglobin level, RBCs, WBCs and platelets counts throughout periods of the first experiment (at 2nd, 4th and 8th weeks from onset of drug administration) as compared with control group.
b) Rats of Second Experiment: (repeated dose 10mg/kg B.wt./week/8weeks)
There was a significant decrease in WBCs count throughout periods of the second experiment (at 2nd and 4th weeks from last drug administration) as compared with control group.
III- Effect of tulathromycin on biochemical findings:
1- Effect of tulathromycin on liver functions:
a) Rats of First Experiment: (single dose 10mg/kg B.wt.)
Rats treated with tulathromycin showed significant increase in ALT, AST and ALP levels in serum allover periods of first experiment (at 2nd, 4th and 8th weeks from onset of drug administration) as compared with control group. While there was a significant decrease in serum albumin level throughout periods of the first experiment (at 2nd, 4th and 8th weeks from onset of drug administration) as compared with control group.
b) Rats of Second Experiment: (repeated dose 10mg/kg B.wt./week/8weeks)
Rats treated with tulathromycin showed significant increase in ALT, AST and ALP levels in serum allover periods of second experiment (at 2nd and 4th weeks from last drug administration) as compared with control group. While there was a significant decrease in serum albumin level throughout periods of the second experiment (at 2nd and 4th weeks from last drug administration) as compared with control group.
2- Effect of tulathromycin on kidney functions:
a) Rats of First Experiment: (single dose 10mg/kg B.wt.)
There was non significant change in serum urea level allover the periods of first experiment (at 2nd, 4th and 8th weeks) as compared with control group. While there was a significant decrease in serum creatinine level only at 4th and 8th weeks from onset of drug administration as compared with control group.
b) Rats of Second Experiment: (repeated dose 10mg/kg B.wt./week/8weeks)
There was a significant decrease in both serum urea and creatinine levels throughout periods of the second experiment (at 2nd and 4th weeks from last drug administration) as compared with control group.
IV- Histopathological alterations induced by tulathromycin:
a) Rats of first experiment: (single dose 10mg/kg B.wt.)
The testes and eididymis of the treated rats revealed normal histological findings allover the periods of first experiment (at 2nd, 4th and 8th weeks).While prostate glands showed interstitial edema and cystic dilatation of some acini filled with eosinophilic secrection and lined by attenuated epithelium.
The liver of the treated rats showed vacuolar and hydropic degeneration of hepatocytes with leucocytic cellular infiltration mainly lymphocytes and macrophages throughout the periods of first experiment (at 2nd, 4th and 8th weeks).
The kidney of the treated rats revealed congestion and degenerative changes with moderate numbers of mononuclear inflammatory cell mainly macrophages and fewer lymphocytes. The glomeruli and large numbers of renal convoluted tubules showed normal histological appearance.
The heart of the treated rats revealed lytic necrosis, with loss of cardiac architecture and replacement of the vacant space with erythrocytes hyaline degeneration of some muscle fibers at 2nd and 4th weeks of First Experiment. While lesions disappeared at 8th week from onset of drug administration. The spleen showed mild lymphoid hyperplasia of white with perivascular leucocytic cellular infiltration mainly lymphocytes and macrophages and focal areas of hemorrhages in the red pulp.
b) Rats of second experiment: (repeated dose 10mg/kg B.wt./week/8weeks)
The testes and epididymis of the treated rats revealed congested blood vessels and mild interstitial edema allover the periods of Second Experiment (at 2nd and 4th weeks).While prostate glands showed interstitial edema and cystic dilatation of some acini filled with eosinophilic secrection and lined by attenuated epithelium.
The liver showed vacuolar and hydropic degeneration of hepatocytes, in addition to mild hyperplastic proliferation of biliary epithelium and formation of newly formed bile ductules were also detected. Also, mild fatty changes of hepatocytes were detected with variable sizes of cytoplasmic vacuoles.
The kidney of the treated rats revealed congestion and degenerative changes, shrinkage and necrosis of glomerular tufts, coagulative and lytic necrosis with presence of Hyaline casts.
The heart of the treated rats revealed Hyaline degeneration of some muscle fibers, small focal areas of zinker’s necrosis accompanied by macrophages infiltration and mild interstitial mononuclear inflammatory cellular infiltration mainly macrophages and lymphocytes in between muscle fibers.
The spleen showed either mild lymphoid depletion or lymphoid hyperplasia of white pulp, apoptosis of some lymphoid cells in the white pulp and focal areas of hemorrhages in the red pulp.
c) Rats of control group:
Rats of this group showed no histopathological alterations.