الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
The beta-lactam antibiotics are widely used in Egypt for the treatment of many cases of acute otitis media, respiratory and urinary tract infections, skin infections, and chlamydia infections. The widely used antibiotic amoxicillin with the trade name ”E-mox” is related to penicillin derivatives group of the beta-lactam antibiotics which inhibits essential enzymes involved in the terminal stages of peptidoglycan biosynthesis important for cell division and growth. In spite of the beneficial effects of this antibiotic, yet some medical reports have been incriminated it for producing certain adverse consequences following its usage.
Hence, the present study was constructed to evaluate the expected side effects of the beta-lactam antibiotic amoxicillin on the pregnant mothers of albino mice and their fetuses. Maternal evaluations included morphological alterations and changes in body weight of confirmed-mated females and maternal pregnancy status. At the 19th day of gestation, the pregnant females of both control and the treated groups were sacrificed and the fetuses were obtained for morphological, skeletal, and histological investigations. The study was also devoted to show any histological and cytological changes which might arise in the body organs, exemplified by two
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essential ones, namely: the liver and the kidney of maternally treated fetuses.
The chosen doses of the used drug in the present study are nearly comparable to the human cumulative therapeutic doses. Therefore, two doses of amoxicillin were used, 205 and 820mg/kg body weight and were considered as the low and high doses, respectively. The selected dosages were nearly correspondent to the human effective low and high therapeutic doses. The pregnant female mice were allocated into three groups. The mice of the first group were considered as the control group and were injected intraperitoneally with the drug solvent (physiological saline solution) for 8 days during gestation from day 7 till day 14. Pregnant animals of the second group were injected similarly with the low dose of the drug (205 mg/kg body weight) for the same period. Pregnant mice of the third group were injected in the same way with the high dose (820mg/kg body weight) of the drug during the same period. During gestation, the body weights of the pregnant mothers were recorded at certain periods in both control and treated groups. At the 19th day of gestation, the pregnant females of both control and the treated groups were sacrificed and the fetuses were obtained for morphological, skeletal, histological and ultrastructural studies.
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Morphological studies
In the present investigation, a conspicuous decrease was recorded in the body weight gain of female mice treated with the antibiotic during pregnancy as compared with the control group. The results showed also that the treatment caused growth retardation (represented by the decrease in body length and body weight) of maternally treated fetuses.
The 19-days old fetuses maternally treated with amoxicillin during gestation days 7-14 showed a mild degree of external malformations characterized by stunting in size, in addition to limb and tail defects. It is worth of mentioning that no morphological malformations were recorded among fetuses maternally treated with the low dose of the drug.
Skeletal studies
The results of the present investigation illustrated that the treatment with the drug caused alternations in several parts of the skeleton of maternally treated fetuses as compared with those of the control group. Incomplete ossification was observed in some bones of the skull, and in the sacral and caudal vertebrae. Delayed ossification extended to the scapula, humerus, radius and ulna as well as the metacarpals and phalanges. A single incidence of skeletal malformation was observed in the vertebral column of 19-days old fetus
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maternally treated with the high dose (820 mg/kg body weight ) of the betalactam antibiotic amoxicillin for 8 days during gestation. This vertebral column anomaly was represented by the abnormal lateral curvature of the vertebral column.
Histological and ultrastructural studies
The liver
The present investigation illustrated that the application of 205 and 820mg/kg body weight of amoxicillin to female mice during pregnancy had induced conspicuous consequences in the histological structure of the liver of fetuses of such treated animals. The major impairments comprised degeneration of the hepatic cells which showed vacuolar degeneration; their nuclei exhibited obvious symptoms of pyknosis, karyorrhexis, and karyolysis. Collection of inflammatory cells are observed dispersed in the hepatic tissue. The severity of such hepatic lesions was correlated with the drug dose. The present investigation showed marked impairments of the hepatic vasculatures of 19-days old fetuses maternally treated with amoxicillin. These lesions include congestion, dilation of the central veins and the surrounding sinusoids and erosion of their endothelial lining cells besides, the activation of the phagocytic Kupffer cells