الفهرس 
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Abstract
Cefotaxime is a third-generation cephalosporin that exhibits saturable plasma protein binding, which influences its pharmacokinetic parameters depending on the dose. Cefotaxime is a broad-spectrum parenteral cephalosporin with potent activity against gram-positive and gram-negative bacteria. Compared to first and second generation cephalosporins,cefotaxime has enhanced activity against many aerobic gram negative bacilli.
The aim of the present work was to study the effect of cefotaxime on some reproductive parameters, some biochemical, histopathological and immunological changes in male albino rats.
In this work, rats were divided into 3 equal groups, each of 15 rats. The first and second groups were injected i.m for 5 consecutive days with cefotaxime at the dose of 80 mg/kg B.wt. and 160 mg/kg B.wt. respectively. The third group was kept as control and injected i.m with 0.2 ml saline/ rat for 5 consecutive days.
The obtained results are summarized as follow:
I-Effect of cefotaxime on some reproductive parameters in male albino rats:
1-Effect of cefotaxime on male reproductive organs weight:
a- The first group (80 mg /kg B.wt.):
Rats treated with cefotaxime showed significant decrease in weight of testes after one and two months post drug administration compared to control group.
The i.m injection of cefotaxime elicited significant decrease in accessory sex organs weight after two, four and eight weeks post drug administration compared to control group.
While there was no significant change in the epididymal weight after two and four weeks but there was significant decrease after eight weeks post drug administration compared to control group.
b- The second group (160 mg /kg B.wt.):
There was a significant decrease in the testes and accessory sex organs throughout all experimental period. There was a significant decrease in epididymal weight after four and eight weeks post drug administration compared to control group.
2-Effect of cefotaxime on semen picture:
a- The first group (80 mg /kg B.wt.)
Cefotaxime administration produced significant decrease in sperm motility percent with increased sperm abnormalities throughout the whole experimental period compared to control group.
While there was significant decrease in sperm cell count only after four and eight weeks post drug administration compared to control group.
b- The second group (160 mg /kg B.wt.):
Cefotaxime administration produced significant decrease in sperm motility percent and sperm cell count with increased sperm abnormalities throughout the whole experimental period compared to control group.
II-Effect of cefotaxime on some biochemical parameters:
Cefotaxime injection in both doses revealed non-significant effect onalbumin level throughout the whole experimental period compared to control group.
There was significant increase in serum urea and creatinine levels throughout the whole experimental period compared to control group.
Cefotaxime administration produced significant decrease in serum total protein and globulin levels throughout the whole experimental period compared to control group.
Serum AST and ALT activities were significantly increased throughout the whole experimental period compared to control group.
III-Effect of cefotaxime on haematological pictures:
Cefotaxime administration in its two dose levels provoked non-significant effect in RBCs, basophilic, neutrophilic, monocytic and eosinophilic counts.
There was a significant decrease in hemoglobin concentration, total leukocytic and lymphocytic counts throughout all experimental period compared to control group.
There was a significant decrease in PCV % after two weeksbut returned back to its normal level after four and eight weeks from drug administration compared to control group.
IV-Effect of cefotaxime on some organs` weights:
There was no significant effect on liver weight after two weeks from drug administration, while there was a significant decrease in liver weight after four and eight weeks post drug administration compared to control group.
Cefotaxime injection at both doses provoked significant decrease in kidney weight only after eight weeks post drug administration compared to control group.
On the other hand, Spleen weight in rats treated with 80 mg cefotaxime /kg B.wt. intramuscularly revealed non-significant change after two weeks from drug administration while therewas significant increase in spleen weight after four and eight weeks post drug administration compared to control group.
While there was significant increase in spleen weight in rats treated with 160 mg cefotaxime/kg B.wt. throughout the whole experimental period compared to control group.
Cefotaxime administration in both doses led to no significant effect on thymus and heart weight throughout the whole experimental period compared to control group.
V- Histopathological findings:
I. Effect of 80mg cefotaxime/Kg B.wt. for 5 successive days:
The male genital organs and accessory glands revealed congested blood vessels and capillaries of the testes. Marked interstitial oedemawas accompanied by congestion of the interstitial blood vessels. Seminiferous tubules revealed degenerative changes of the lining epithelium in the form of vacuolar and hyDROPic degeneration accompanied by incomplete spermatogenesis of some seminiferous tubules.
The livers of the treated rats showed congestion of the central veins and portal blood vessels,degenerative changes of the hepatocytes in the form of vacuolar and hyDROPic degeneration and focal areas of mononuclear cellular aggregation.
The Kidney of rats showed vacuolar and hyDROPic degeneration of the lining epithelial cells of some renal convoluted tubules.
The lungs showed congestion of the peribronchiolar blood vessels and perialveolar capillaries together with hyperplasia of the peribronchiolar lymphoid follicles.
The spleen showed congestion of the splenic blood vessels and multiple focal areas of hemorrhages in the red pulp and lymphoid depletion of the white pulp.
The thymus revealed congested blood vessels and mild interstitial oedema in medulla.
II. Effect of 160mg cefotaxime /Kg B.W. for 5 successive days:
The male genital organs and accessory glands revealed congested blood vessels in addition to degenerative and necrobiotic changes of the lining epithelium of some of the examined organs.
The testes showed severe congestion of testicular blood vessels and the interstitium was edematous.Vacuolation of the lining epithelial cells of some seminiferous tubules (degeneration) accompanied by incomplete spermatogenesis.
The livers of the cefotaxime - treated rats showed congestion of the central veins, portal blood vessels and hepatic sinusoids and diffuse hyDROPic degeneration with coagulative necrosis of the hepatocytes.
The examined kidneys revealed congested blood vessels and dilatation of some renal convoluted tubules
The lungs showed congestion of the pulmonary blood vessels together with slight hyperplasia of the peribronchiolar lymphoid follicles and focal areas of alveolar emphysema
The spleen of rats revealed multiple focal areas of hemorrhages in the red pulp with mild lymphocytic cellular infiltration.
The thymus of treated rats showed lymphoid depletion associated with focal areas of coagulative necrosis in the thymic cortex.
III. Non treated control Rats:
Rats of this group showed no histopathological alterations.
VІ - Immunological findings:
Cefotaxime injection in both dose levels revealed a significant decrease in phagocytic activity and phagocytic index after 2nd week post drug administrationbut returned back to normal level after eight weeks from drug administration compared to control group.
CONCLUSION
It could be concluded that third generation cephalosporins must not be the first choice antimicrobial agents in animals and should be reserved for use where susceptibility testing indicates that alternative are not available and for serious, life-threatening infections caused by Gram-negative bacteria.
Cefotaxime administration induced fertility troubles in the form of abnormal semen characters and decreased reproductive organs weight. Moreover cefotaximeadministration provoked some adverse effects on haematological,biochemical and immunological parameters so attention should be paid to administration of higher doses of cefotaxime.