الفهرس 
Introduction and aim of the workOnly 14 pages are availabe for public view
 |  | from | 226 |  |  |
| | | from | 226 | | |
Abstract
The present study deals with teratogenic effects which occur in pregnant mice and their fetuses after intragastric administration of sodium benzoate that is commonly used in Egypt as an antimicrobial agent in food industry. The used low and high doses of SB were 200 and 500 mg/kg b.wt. Fifty pregnant mice were divided into four groups each group subdivided into two sub-groups for treatment with low and high doses of SB. The control group (C) consisted of seven animals were administered distilled water by stomach tube for five successive days. Frist treated group (G1 ) consisted of fourteen animals subdivide in two groups treated with low and high doses of sodium benzoate from day 3 of gestation to day 7 , the second group (G2) treated with low and high doses from day 8 of gestation to day 12, the third group (G3) treated with high and low doses from day 12 to day 16 of gestation . All females sacrificed on day 18 of gestation and the following parameters are concerned: 1) DeterminationThe average increase in the maternal body weight. 2) Determination the total number of alive and dead fetuses. 3) The external abnormalities of fetuses, fetal weight and fetal length and skeletal examination were also studied. 4) Histopathological examination of the liver and kidney of the mothers and their fetuses . 5) Ultrastructural observations of the liver and kidney of mothers of the second group (G2) treated with high dose of SB were investigated. The present study showed that : 1) Sodium benzoate significantly reduced the maternal body weight gain during gestation and body weight and length of their fetuses. 2) This study revealed that most elements of fetuses skull showed moderate malformations. Ossification of the centra of some cervical vertebrae was absent especially at the high dose in G2. The high dose of sodium benzoate caused some unossified caudal vertebrae especially in G2 and (G3). The whole sternum and xiphoid cartilage became shorter than the control in all groups treated with both doses. The cartilaginous portion of the ribs exhibited less blue coloration than the control denoting reduction in its chondrification. However, some ribs showed curled appearance. In addition, the scapula and clavicle were shorter and less thickened in all treated groups. The long bones of the fore and hind limbs were shorter in length and decreased in thickness compared to the control. In such case, the density of red coloration was less than the control. 3) Treatment of pregnant mice with this substance revealed histopathological changes, which were more severe in mice given the high dose of sodium benzoate. (A) Liver The most obvious histological changes appeared in the liver of treated mothers marked signs of degenerative changes of the hepatic tissue. Dilation of blood sinusoids and severe congestion of blood vessels were also observed. Leucocytic infilteration was seen invaded the damaged area, marked hyperplasia of sinusoidal kupffer cells, and focal necrotic hepatocytes were shown .In some degenerated areas, the liver cells appeared structurless with ill-defined cellular boundaries and pyknotic or chromatolytic nuclei. The liver tissue of maternally treated fetuses showed degenerative alterations represented by highly vacuolated hepatocytes with vacuolated and pyknotic nuclei. Chromatolytic nuclei were oftenlly observed. Dilated blood sinusoids and blood vessels showed numerous blood cells in their lumina. Usually, the cytoplasm of the highly vacuolated cells was observed restricting to small area around the nucleus and in some instances the nuclei were seen displaced away from the cell center and found very near to the cell envelope. Very highly dilated blood vessels and spaces in the liver tissue were seen occluded with red blood cells denoting a kind of hemorrhage which appeared also in other areas of the liver tissue. Electron microscope examination revealed significant alterations in the hepatocytes of treated mothers. The cytoplasm of hepatocytes showed numerous large vacuoles of different sizes and shapes. The hepatocytes showed fatty changes indicated by the presence of large lipid droplets in the cytoplasm. The mitochondria exhibited condensed opaque matrices without any internal organization and the blood sinusoids revealed dilations, congestions and activated kupffer cell. A more advanced stage in the nuclear degeneration was also observed B) Kidney Histological observation of the kidney of treated mothers showed showed hydropic degeneration of the cytoplasm, deformation of the proximal and distal convoluted tubule cells and occurance of intratubular casts. Also, the nuclei showed some sort of degeneration. Areas of lymphocytic infiltration and hemorrhage were detected in the cortical reigon. In addition, atrophied renal corpuscles and degenerated glomeruli were detected. The epithelia of the visceral and parietal layers of some Bowman’s capsule were degenerated and the urinary spaces were dilated. .Low and high doses maternally treated fetal kidneys showed degenerative changes in the epithelial cells lining the renal tubules. Also, atrophied and degenerated glomeruli were detected in fetuses maternally treated with high dose of SB. Electron microscope examination of sections of the kidney showed congested glomerulus capillaries leading to narrowing of the urinary space. The mesangium was increased and spread around the mesangial cells. Some of the capillary endothelial cells were hypertrophied and protruded in the capillary lumina. The proximal convoluted tubule cells revealed variable degrees of pathological alterations. Cells showed thick basement membrane, intact microvilli, dense cytoplasm, degenerated mitochondria, few vacuoles, some luminal vesicles and electron dense pyknotic nuclei. The distal convoluted tubules showed various signs of pathological alterations. Some tubules were dilated, others were collapsed with very narrow slit like lumina. The distal tubule cells lost their characteristic shapes and became flattened, elongated or rounded. The cytoplasm revealed electron dense degenerated mitochondria with dense matrices from the findings of the present study and the aforementioned studies, it can be suggested that the embryo toxicity of sodium benzoate may be due to malnutrition or mother toxicity or fetotoxicity through the placental passage of SB or its metabolites.